Lightning was in the area. The appropriate answer was one final booming serve from the 6-foot-9 Isner.
Isner had 20 aces as he survived another challenge to his endurance, beating the heat and Anderson 6-3, 6-7 (7-9), 6-3 to advance to the Atlanta Tennis Championships final on Saturday.
With the siren wailing, Isner unleashed a service winner to end the match.
Isner will face the winner of Saturday night's match between top seed Andy Roddick and Mardy Fish in Sunday's final.
Isner gained fame by winning the longest match in history, a three-day, 183-game match at Wimbledon last month. The Atlanta semifinal, played about an hour from his University of Georgia college home, presented a different level of stress for Isner.
The temperature was 96 degrees for the start of the match. On the hard-court surface, the reading reached 147 degrees.
"The conditions were just brutal," Isner said. "It definitely took a lot out of me."
Isner said he relied on his "will to win."
"Even though I am exhausted, I am able to use my energy smartly," he said. "I am able to keep plugging away until I get my break eventually."
Anderson said he went through six or seven shirts and had one drying on a fan if needed. But sweat-soaked shirts were not the only concern.
"I was sweating through my shoes," Anderson said. "I was slipping quite a bit."
Isner beat the 6-foot-8 Anderson of South Africa in a matchup of two of the three tallest players in the ATP World Tour's top 100 rankings.
The two were college rivals. Isner beat Anderson as Georgia beat Illinois to win the 2007 NCAA championship. Isner is 3-1 as a professional against Anderson.
Anderson provided a stiff challenge from the opening game, when he had a break point on Isner. Setting the pace for the match, Isner rallied to win the game. He saved each of the seven break points he faced in the match.
Isner appeared the most affected by the intense heat in the second set. He couldn't hold serve when leading 7-6 in the tiebreaker. Anderson won two straight points off Isner's serve and then took the set.
The break between the second and third sets combined with cloud cover to give Isner a lift. The shade from the clouds dropped the on-court temperature about 30 degrees.
Isner led 4-3 in the third set before breaking Anderson's serve for a 5-3 lead.
Then came the weather siren on Isner's final serve.
"We didn't know how long that was going to last," Anderson said. "We just had to keep on playing. It kind of started just as he was starting to serve, which was kind of funny timing."
Isner said he wasn't worried about the threat of bad weather.
"I wasn't even thinking that," he said. "I was just trying to get the hell off the court."