BOSTON -- Perhaps sensing that this was the chance to get the Red Sox back into the game, David Ortiz unloaded on a 2-2 pitch from Indians lefty reliever Brad Fultz and sent a momentary surge of excitement around Fenway Park. The ball was high and deep and -- foul. And just like that, the air went out on any realistic hopes of a comeback in what wound up an 8-4 loss to the Indians on Wednesday night.

"It was a changeup and I just hooked it," said Ortiz.

If Ortiz's bid for a two-out grand slam in the bottom of the seventh inning had been successful, the game would have instantly been tied on one swing. Instead, he tailed it a couple of feet to the wrong side of Pesky's Pole before ending the frame with a looping liner to third baseman Casey Blake. An inning that started with the bases loaded and nobody out ended with no runs.

There was no rescuing the Red Sox on a night Daisuke Matsuzaka opened with four shutout innings, only to be touched up for six runs before his departure with two outs in the sixth. Over 5 2/3 innings, the right-hander was belted for 12 hits, walking none and striking out four. He threw 106 pitches.

The Indians left town with one win in the three-game series against the 36-16 Red Sox, who saw their five-game winning streak snapped.

Five days after a flu-ridden Matsuzaka willed his way through five innings and a win against the Rangers, the right-hander was back to full health in this one, but he just couldn't get the job done. Dice-K was not in the mood to make excuses that the sickness was still an issue.

"I don't think there was any specific effect," said Matsuzaka. "I was able to prepare for this start like I usually do. As I mentioned before, I felt better right away, so I don't think there is any particular residual fatigue."

Ortiz wasn't tired either. He just returned to the lineup after missing three days with tightness in his hamstrings. But instead of adding yet another clutch home run to his seemingly endless list, Ortiz instead saw his home run drought stretched to 16 games, his longest since joining the Red Sox.

The reaction from the Red Sox dugout when Ortiz's long foul first took flight?

"Hoping," said Red Sox manager Terry Francona. "Watching the at-bat, he was probably going to have to hit one to left field, because that was probably all they were going to give him. He fouled some pitches off, but they were away. Then he laid off enough and saw enough pitches and got one to handle, but pulled it foul."

Though it was hard to remember by the time the night was over, it was the Red Sox who had the early momentum, striking first in the bottom of the second against the soft tosses of Paul Byrd. Boston got a break as J.D. Drew led off the inning by reaching on an error by second baseman Josh Barfield. Mike Lowell cranked a double to left. Jason Varitek broke the scoreless tie with a fielder's-choice grounder to second.

Back came the Sox in the fourth. Manny Ramirez led off with a double to right and moved to third on a wild pitch. That enabled him to score on Drew's fielder's-choice grounder.

Matsuzaka was strong early, getting out of a bases loaded, one-out jam in the first and took a 2-0 lead into the fifth. From there, it was all Cleveland. Blake drove home Cleveland's first run with a fielder's choice and Travis Hafner tied the game at 2 with a double into the gap in left-center.

"Not only my fastball, but, overall, I think I had problems with my control," Matsuzaka said.

The Indians pounced again in the sixth. Trot Nixon got it started with a ground-rule double to right. David Dellucci slammed a one-out double to left to put Cleveland ahead for the first time at 3-2. But the crushing blow was landed by Grady Sizemore, who hammered a two-run homer into the bullpen in right, opening up a four-run edge for the Indians.

"I don't think he located his fastball like he has and like you need to against a team like Cleveland with that lineup," said Francona. "[He] left a slider over the plate to Sizemore for the home run. Against a lineup like that, if you don't consistently make pitches, they have that chance to hurt you."

The pitch to Sizemore was Matsuzaka's last of the night.

One trend continued for Matsuzaka in this one. On those nights he's struggled, it has typically been one bad inning that has caused his undoing.

"It's been different things," said Varitek. "We've gotten burnt on different pitches each time. I don't think it's that much as much as just getting over the hump and getting through an inning. He's gotten through innings like that too, very much so."