At just 4-foot-11, Barbara Mikulski (search) starts her news conferences by stepping onto a stool behind the podium. But almost no one underestimates her when she opens her mouth.

The longest-serving woman now in the U.S. Senate, Mikulski has become known for her fiery straight talk and bulldog advocacy for her home state.

When a maximum-security federal prison was slated to go up next a historic black community just outside Baltimore, the Democrat fired up a crowd by promising to slash it from a bill "with my red pen." Three days later, the project was ditched. More recently, at Mikulski's demand, NASA (search) agreed to reconsider its decision to abandon the Hubble Space Telescope.

"At first blush, she looks invulnerable," said Maryland pollster Keith Haller.

And by all accounts, she will probably prove invulnerable when she runs for re-election in November. But the Republicans might just put up their best fight in decades.

The GOP is running political novice E.J. Pipkin (search), a 47-year-old self-made millionaire.

"People feel it's time for a change. Twenty-seven years is enough," he said. "It's time for new people with new ideas and a new energy level. She's had her chance at bat; let someone else take a crack at it."

Though he has served only a year in his first public office - state senator - Pipkin won by overthrowing a 24-year Democratic incumbent. He and his wife knocked on 10,000 doors, he says, and waved signs from the bed of his red pickup truck.

He made his fortune working for 16 years as a bond salesman on Wall Street. He spent $600,000 on his state Senate campaign.

"He is an aggressive campaigner, and if he's willing to spend some money, it'll at least make for an interesting race," said Patrick Gonzales, whose polling firm found only 30 percent of Marylanders surveyed in October had heard of Pipkin.

He faces an uphill battle against Mikulski, a 67-year-old dynamo seeking her fourth term in the Senate after five terms in the House. She is known for fighting hard for industries near and dear to Maryland's economy.

Last month, she told the NASA administrator she would "not take no for an answer" when fighting to protect the Hubble, a project that brings work to 550 astronomers and others at a Baltimore science institute.

She first won elected office three decades ago after saving Baltimore's historic Fells Point (search) neighborhood from being flattened for a highway project. She has not faced a serious challenger since. In her last two elections, in 1998 and 1992, she got 71 percent of the vote against conservative commentator and one-time presidential contender Alan Keyes (search) and Ross Pierpont (search), a frequent, and always unsuccessful, candidate for office.

As for Pipkin, "in the best case, it still will be tough for him to defeat her," Gonzales said. "But instead of 60 percent to 40 percent, he could push it to 55 percent to 45 percent, in that range."

For this race, Pipkin put in $250,000 of his own money and has since raised $210,000 from about 2,000 donors, he said. He is buying advertising time on 49 radio stations and launched a TV ad campaign two weeks ago. But his half-million does not approach Mikulski's $2 million coffer.

Haller does not give Pipkin much of a chance, but said Mikulski will not dismiss him.

"Any good politician will take an opponent who's got personal financial resources seriously," Haller said. "We've seen that out west in California, where people writing a check for $10 million can change the political landscape."

Mikulski will not talk about her challenger except to say he attacks her instead of coming up with ideas for the state. He accuses her of acting like a moderate friend of the middle class but voting like a liberal.

But Marylanders tend to connect with brusque Mikulski's personality on a visceral level, Haller said. As a result, "people tend not to dissect her particular positions on issues and ideologies."

"That's why her popularity has remained so high and she's managed to avoid the ups and downs that come with changing political times," he said.