SAN FRANCISCO (AP) — Barry Zito understands how unpredictable a game baseball can be. Making his first start in three weeks only added to the mystery for the Giants left-hander.

Zito failed to get out of the fourth inning and San Francisco lost 12-1 to the Boston Red Sox on Wednesday.

“I was excited to get the ball,” Zito said. “Some strange stuff happened out there today. Baseball is a strange game sometimes. The nature of the game is so unpredictable. That’s why we all love it and why we all hate it. You never know what you’re going to get when you come to the yard.”

Zito gave up a two-run home run to Will Middlebrooks with two outs in the second and the pitcher on deck.

“We’re not happy about the way we played,” Zito said. “It’s fundamental baseball. That homer is on my back.”

The Giants also made two errors, messed up a bunt play and allowed a ball to fall safely between three fielders.

“That’s kind of a freak play,” Giants first baseman Brandon Belt said of the base hit in shallow right field that led to three runs in the third. “You work on that stuff in spring training. People have to communicate and we didn’t do that.”

Zito (4-9) lasted 3 2/3 innings in his first start since July 30. He allowed six runs on seven hits, walked two and struck out three.

“We didn’t play well at all,” Giants manager Bruce Bochy said. “We’re having a hard time with the bats here. It’s got to get better with the pitching side and the hitting side.”

Joaquin Arias homered among his two hits for the Giants, who have lost three of four.

“Not a whole lot went right today,” Giants catcher Buster Posey said. “We have to come out tomorrow and be ready to go. You try to forget these games and even the good ones you put behind you and get ready for the next day.”

Felix Doubront (9-6) rebounded from a tough outing to pitch eight strong innings for the Red Sox, who have won three of five and entered play in a virtual first-place tie with Tampa Bay in the AL East. Doubront gave up one run on five hits. He walked one and struck out three.

Jacoby Ellsbury and Shane Victorino each had three hits for Boston, with Victorino driving in a run. Ellsbury scored twice and got his league-leading 46th stolen base. Dustin Pedroia added two hits and drove in a run.

“Any time you get hits out of the top of the lineup good things can happen,” Victorino said. “We just have to keep it going.”

The Giants have allowed 10 runs or more in four interleague games, their most in any season.

Zito, the 2002 Cy Young winner, is 0-25 in 29 games in which he has allowed six or more runs in a San Francisco uniform. He never allowed more than six runs in a game with the Oakland Athletics.

NOTES: Zito owns a career mark of 5-7, with a 5.52 ERA, in 15 games against the Red Sox. ... RHP Matt Cain (8-8, 4.35) will start for the Giants on Thursday night against Pittsburgh. ... The Giants went 0 for 15 with runners in scoring position this series. ... The Giants have gone 0-4-1 in their last five series at home. ... LHP Mike Kickham allowed six runs in four innings, the most by a Giants reliever this season.