Thousands of residents calmly fled Monday from the mesa-top town that's home to the Los Alamos nuclear laboratory, ahead of an approaching wildfire that sent up towering plumes of smoke, rained down ash and sparked a spot fire on lab property where scientists 50 years ago conducted underground tests of radioactive explosives.

Los Alamos National Laboratory officials said that the spot fire was soon contained and no contamination was released. They also assured that radioactive materials stored in various spots elsewhere on the sprawling lab were safe from flames.

The wildfire, which began Sunday, had destroyed 30 structures south and west of Los Alamos by early Monday and forced the closure of the lab while stirring memories of a devastating blaze in May 2000 that destroyed hundreds of homes and buildings.

"The hair on the back of your neck goes up," Los Alamos County fire chief Doug Tucker said of first seeing the fire in the Santa Fe National Forest on Sunday. "I saw that plume and I thought, 'Oh my God here we go again.'"

Tucker said the current blaze — which grew Monday to roughly 44,000 acres, or 68 square miles — was the most active fire he had seen in his career. By midafternoon, it had jumped a highway and burned an acre of land on the outskirts of the lab's 36-square mile complex.

The fire scorched a section of what is known as the Tech Area, 49, which was used in the early 1960s for a series of underground tests with high explosives and radioactive materials. Lab officials said the fire was safely extinguished.

Lab spokesman Kevin Roark said environmental specialists from the lab were mobilized and monitoring air quality on Monday, but that the main concern was smoke.

The anti-nuclear watchdog group Concerned Citizens for Nuclear Safety, however, said the fire appeared to be about 3 1/2 miles from a dumpsite where as many as 30,000 55-gallon drums of plutonium-contaminated waste were stored in fabric tents above ground. The group said the drums were awaiting transport to a low-level radiation dump site in southern New Mexico.

Lab spokesman Steve Sandoval declined to confirm that there were any such drums currently on the property. He acknowledged that low-level waste is at times put in drums and regularly taken from the lab to the Waste Isolation Pilot Project site in Carlsbad.

Sandoval said the fire was "quite a bit away" from that storage area. But he could not say what would happen if drums containing such waste were to burn.

"Unfortunately, I cannot answer that question other than to say that the material is well protected. And the lab — knowing that it works with hazardous and nuclear materials — takes great pains to make sure it is protected and locked in concrete steel vaults. And the fire poses very little threat to them."

Sen. Tom Udall, D-N.M., who was visiting evacuees at the Santa Claran Hotel Casino in Espanola, said "there's no doubt" the lab stores a variety of hazardous and radioactive materials that "you don't want to escape in the atmosphere." But he said he was confident lab and state environmental officials had monitoring systems in place to "evaluate exactly what we're seeing here."

Traffic on Trinity Drive, one of the main roads out of Los Alamos, was bumper-to-bumper Monday afternoon as residents followed orders to leave. Authorities said about 2,500 of the town's roughly 12,000 residents left under an earlier voluntary evacuation.

"We're just hoping for the best," Vivian Levy, a resident since the 1970s, said as she packed her car and her animals — again.

"Last time, I just walked out of my house and said goodbye, and that it was going to be OK," she said before breaking down in tears. "I'm doing the same thing this time. It's going to be OK. I'm prepared to say goodbye."

Sam Kendericks said he knew the blaze was going to be bad when he first saw the plume Sunday.

"I was going to the hardware store and I did a U-turn as soon as I saw the plume come over the mountain. I told my wife to start packing. We were here 10 years ago. We had 20 minutes last time. So this time we're ready," he said.

The fire has the potential to double or triple in size, Tucker said, and firefighters had no idea which direction the 60 mph-plus winds would take it.

"We are preparing for the fire to go in any direction," Tucker said.

On Monday afternoon, the flames were just across the road from the southern edge of the famed northern New Mexico lab, where scientists developed the first atomic bomb during World War II. The lab activated its emergency operations center overnight and cut natural gas to some areas overnight as a precaution.

In 2009, the U.S. Department of Energy's inspector general issued a report that said Los Alamos County firefighters weren't sufficiently trained to handle the unique fires they could face with hazardous or radioactive materials at LANL.

Lab and fire department officials at the time said the report focused too much on past problems and not enough on what had been done to resolve them. Some problems also were noted in previous reports.

On Monday, lab and fire officials said they were confident that if the flames reached lab property they would be able to protect its sensitive facilities.

"We're in a much better place than we were 11 years ago," said Rich Marquez, executive director of the lab, noting the lab has thinned out potential fire hazards and has enacted a number of emergency protocols.

"Our day to day activity is about appropriate stewardship of those resources. We take precautions just in our normal existence and the way we plan, the way we manage materials like that. We assume the worst."

The lab, which employs about 15,000 people, covers more than 36 square miles and includes about 2,000 buildings at nearly four dozen sites or "technical areas." Those include research facilities as well as waste disposal sites. Some lab facilities, including the administration building, are in the community of Los Alamos while others are several miles away from the town.

Greg Mello, with the anti-nuclear watchdog Los Alamos Study Group, said the group doesn't have enough information "to formulate any views on safety at this point."

"It is important to remind ourselves that the site has natural hazards ... and Murphy's Law is still about the best enforced law in the state," he said.

The blaze also was threatening Frijoles Canyon, which is home to a number of sacred Native American archaeological sites. Also threatened, Tucker said, was the recently restored Bandelier National Monument.

At least 30 structures had burned south of Los Alamos overnight, but Tucker said it was unclear exactly how many of those were homes.

The blaze started on private land about 12 miles southwest of Los Alamos and quickly grew. Flames and smoke could be seen from the outskirts of Albuquerque, about 80 miles away. A cause wasn't immediately known.

The fire was eerily similar to one of the most destructive fires in New Mexico history. That fire, the Cerro Grande, burned some 47,000 acres — 73 square miles — in May 2000 and caused more than $1 billion in property damage. About 400 homes and 100 buildings on lab property were destroyed in that fire. That blaze also raised concerns about toxic runoff and radioactive smoke, although lab officials said no contaminants were released during it.

Another fire continued to burn uncontrolled on the other side of Santa Fe. The Pacheco fire near Santa Fe has burned about 9,900 acres and is 10 percent contained, according to the Forest Service. And about 125 acres were burning south of Albuquerque along the Rio Grande bosque.

Meanwhile, the biggest blaze in Arizona history was 82 percent contained after burning through 538,000 acres in the White Mountains in northeast Arizona. The fire started May 29 and has destroyed 32 homes. It's believed to have been caused by a campfire.

And in Colorado, about 100 firefighters are battling a wildfire that broke out in a canyon northwest of Boulder.___

Associated Press writers Jeri Clausing in Albuquerque, Barry Massey in Santa Fe and P. Solomon Banda in Espanola contributed to this report.