LOS ANGELES -- It was hardly lost on Johan Santana that on Wednesday evening, after a highly publicized six-week slump, David Ortiz whacked his first home run of the season out of Fenway Park. Still fresh on Santana's mind, nearly three years later, is the game in which Santana served up Ortiz's Red Sox-record 51st home run of the 2006 season.

"The only way I wasn't going to give up a home run to him was not to throw the ball," Santana said that day.

But since then, times have changed. Ortiz's homer was his first this year, a sign that his reign of success in the American League is sputtering. And Santana is pitching as well as he has at any point in his career, all but carrying the Mets through the first six weeks of this season.

There will be no foregone conclusions when the Mets head into Fenway Park Friday night for the first of three games against the Red Sox -- their latest foray into Interleague Play. But the Mets hardly hope that Ortiz will reprise that record-breaking home run.

Instead, the Mets will be rooting for Santana to continue the otherworldly pitching he has displayed over the first third of this season, in a ballpark that nearly became his home.

For a time in the winter following the 2007 season, the Red Sox -- not the Mets -- were the front-runners to trade for Santana and sign him to a long-term deal. How different things would have been.

"It's a great ballpark, a great atmosphere," Santana said of Fenway. "The fans are really into the game. It's definitely an old-school ballpark with a great atmosphere."

Throughout the three games at Fenway, Mets manager Jerry Manuel will rotate David Wright, Carlos Beltran and Gary Sheffield at the designated hitter spot in an attempt to give each of them a half-day off. Now that Daniel Murphy will be playing regularly at first base, Manuel said that Sheffield will receive the bulk of the playing time in left field.

The Mets haven't played the Red Sox since dropping three straight at Fenway in 2006. In that series, Ortiz was 4-for-10 with a home run and a double.

Opposing Santana in Friday night's game will be Daisuke Matsuzaka, who was still pitching for the Seibu Lions of Japan's Nippon Professional Baseball League in 2006. Matsuzaka will be making his first start since a dead arm forced him to the disabled list in mid-April.

Pitching matchup
NYM: LHP Johan Santana (5-2, 1.36 ERA)
Undermined by his defense yet again, Santana nonetheless pitched seven efficient innings and allowed six runs -- four of them earned, and only two of them completely deserved -- last Saturday against the Giants. Still, the damage was enough to nearly double his ERA, from 0.78 to 1.36. Santana's next start will come against the Red Sox, the team he was nearly traded to after the 2007 season. He has not faced the Sox since then, but he is 1-3 with a 6.89 ERA in his career at Fenway Park.

BOS: RHP Daisuke Matsuzaka (0-1, 12.79 ERA)
Matsuzaka makes his long-awaited return to the mound after being on the disabled list since April 15 with a right shoulder strain. The right-hander, an 18-game winner last year, was 0-1 with a 12.79 ERA in two big league starts early this season but has looked sharp in his Minor League rehabilitation outings. He made his third rehab start with Triple-A Pawtucket at Toledo on May 15 and threw five innings (70 pitches, 48 strikes), yielding two runs on three hits and a walk and striking out nine.

Tidbits
Catcher Brian Schneider took one at-bat in an extended spring training game Wednesday, his first competitive at-bat since landing on the disabled list with a strained back muscle April 16. ... With a single in the sixth inning on Wednesday, Wright extended his hitting streak to 12 games. ... The only active Mets with histories against Matsuzaka are Sheffield, who is 6-for-11 with a home run and two doubles, and Jeremy Reed, who is 0-for-3. ... Right-handed reliever Nelson Figueroa cleared waivers Wednesday. The Mets outrighted him to Triple-A Buffalo.

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Up next
• Saturday: Mets (Mike Pelfrey, 4-1, 4.61) at Red Sox (Josh Beckett, 4-2, 5.85), 7:10 p.m. ET
• Sunday: Mets (Tim Redding, 0-0, 3.00) at Red Sox (Tim Wakefield, 5-2, 3.59), 1:35 p.m. ET
• Monday: Mets (John Maine, 3-3, 4.53) vs. Nationals (TBD), 7:10 p.m. ET