CHICAGO -- Philip Humber followed up the best day of his career with one of his worst.
Youkilis, mired in an early-season slump, hit his second career slam into the right-field bullpen during a five-run third inning against Humber, who was making his first start since pitching a perfect game in a 4-0 victory at Seattle on Saturday.
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"I got a lot of pitches up over the plate," Humber said. "To a team like that, they make you pay for it."
It didn't take long for Humber (1-1) to falter. He walked leadoff batter Mike Aviles in the first, snapping his streak of 29 consecutive batters retired.
One out later, the right-hander allowed a single to Dustin Pedroia, a dribbler up the third-base line that was the first hit off Humber since Nick Markakis' one-out double for Baltimore in the fifth inning of the Orioles' 10-4 victory at Chicago on April 16.
"We had our reports on watching Phil," Youkilis said. "He's a guy who's going to throw strikes and go at you. You have to be ready to hit."
Humber was tagged for a career-high nine runs and eight hits in five innings. The nine earned runs he allowed after his perfect game were a record, topping the eight given up by Jim "Catfish" Hunter after his perfecto for Oakland in 1968.
"This game will humble you, man," Humber said. "It will make you feel good one day and make you feel real bad the next. You've got to take every game as its own game."
Johnny Vander Meer remains the only major league pitcher to throw consecutive no-hitters, accomplishing the feat in 1938 with Cincinnati.
It has been a hectic week for Humber, who did a segment on David Letterman's show among many media-related appearances this week. Also, his wife Kristan is expecting the couple's first child in the next couple of weeks.
"I stayed with my normal routine," Humber said. "I did my best to eliminate the distractions. I felt like I was focused on the game.
"I don't think anything that happened Saturday affected tonight," he added. "It was just a bad day. I'll just chalk it up to one of those days and hopefully next time will be better."
The resurgent Red Sox have scored 34 runs in winning their last four games, a streak coming on the heels of a five-game skid.
"The offense is playing extremely well," Boston manager Bobby Valentine said. "A combined effort, no one trying to do too much. That's good offense. That's playing baseball the right way."
After throwing just 96 pitches to complete his masterpiece, Humber twice needed more than 30 pitches to get through an inning. He threw 92 pitches over the first four innings.
Saltalamacchia followed Youkilis' slam with a home run just inside the right-field foul pole. He added a two-run shot in the fifth off Humber, his fourth homer of the season.
Humber allowed three walks and three home runs. His ERA rose from 0.63 to 4.66.
Youkilis singled and scored in the fifth and added an infield single in the eighth. His three hits, two runs and four RBIs were an encouraging sign for a hitter that entered the game batting only .204. The grand slam was his second home run of the season and only his second during his past 28 games dating to Aug. 14, 2011.
"I'm having better at-bats and doing little things here and there," Youkilis said. "I look at it as a long season, and you're going to go through stuff. Hopefully the bad at-bats are a thing of the past."
Boston starter Felix Doubront (1-0) wasn't sharp but picked up his first big-league victory since Aug. 10, 2010. He allowed five hits and three walks, threw a wild pitch and hit a batter with a pitch, but limited the White Sox to three runs in six innings.
Junichi Tazawa tossed three scoreless innings for his first major league save.
Chicago's Dayan Viciedo broke out of a 1-for-16 slump with two hits, including a leadoff home run in the fourth. All three of his RBI this season have come on solo home runs.
- Andre Rienzo, a pitcher in the White Sox farm system, was suspended for 50 games after testing positive for a banned substance.
- Marlon Byrd started in center for the Red Sox in his first game in Chicago since being acquired from the crosstown Cubs on Saturday.
- White Sox manager Robin Ventura said he didn't plan to use reliever Jesse Crain out of the bullpen for precautionary reasons. Crain hasn't pitched since April 20 because soreness in his left oblique, but Ventura doesn't expect him to go on the disabled list.