TORONTO -- Mark Reynolds made his first hit of the new season a winner.
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"I'm just happy I got my first hit," said Reynolds, who was 0 for 7 with three strikeouts before his big blast. "I didn't care if it was a go-ahead homer or not."
Reynolds drilled a leadoff shot into the second deck off Sergio Santos (0-1), the fifth Blue Jays reliever.
"He's going to miss sometimes, but when he does that, it's a game changer and it was tonight," Indians manager Terry Francona said of Reynolds, who set a major league record with 223 strikeouts in 2009.
"That was a big hit for us," Perez said of Reynolds' homer. "He crushed it."
The overhauled Blue Jays lost their second straight to begin the season. Toronto's offense has just three runs and nine hits in two games.
"This team's built to score runs," Blue Jays manager John Gibbons said. "We haven't done that yet. But we're going to hit."
Toronto dropped its first two games of the season for the first time since an 0-3 start in 2004, but Bautista denied that high expectations were causing the Blue Jays to press.
"No," he said. "That's a big N-O. Both capital letters."
Cleveland's Michael Brantley went 4 for 5 with an RBI, the fifth four-hit game of his career.
The Indians took a 2-1 lead in the eighth against reliever Darren Oliver. Nick Swisher led off with a walk and moved to second on Brantley's fourth single. Carlos Santana hit a grounder to third, where Swisher was forced out, but Maicer Izturis' throw to first sailed wide, allowing Brantley to score.
Bautista tied it with a one-out shot to left off Perez in the ninth. Bautista had gone hitless in his first three at-bats, grounding into a pair of inning-ending double plays.
After Bautista swung and missed a first-pitch slider, Perez tried to sneak a fastball past the Blue Jays slugger.
"I had good movement on it," Perez said. "It just caught too much of the plate."
The Indians opened the scoring in the third. Michael Bourn led off with a double just beyond the reach of Izturis at third. Two outs later, Swisher walked and Brantley followed with an RBI single between third and short.
Izturis tied it in the bottom half with a leadoff drive to right, his first, and Toronto's first homer of the new season.
Cleveland starter Ubaldo Jimenez, who lost a career-high 17 games last season and ended the year with nine straight road losses, looked sharp in his season debut.
"I thought he was outstanding," Francona said. "His secondary stuff, his direction to the plate was down. His offspeed, especially his changeup, was really good."
Jimenez allowed one run and three hits in six innings, walked two and struck out six.
"I felt really good," Jimenez said. "That's a tough lineup. They have everything. They can run, they can hit for power."
Brantley and Santana hit consecutive singles in the sixth, but Blue Jays starter Brandon Morrow ended his outing by getting Reynolds to ground into a double play.
Morrow allowed one run and six hits in six innings. He walked two and struck out eight.
- Indians LHP Scott Kazmir will miss his first scheduled start of the season, Saturday at Tampa Bay, because of a sore abdominal muscle on his right side. Kazmir will return to Cleveland for tests and rejoin the team before Friday's game against the Rays.
- The Indians claimed right-hander Robert Whitenack on waivers from the Chicago Cubs and optioned him to Double-A Akron. Cleveland also transferred RHP Frank Herrmann (right elbow) to the 60-day DL.
- Blue Jays manager John Gibbons said backup Henry Blanco will "probably" catch the next start by knuckleballer R.A. Dickey. Arencibia had three passed balls in Dickey's debut Tuesday.
- Attendance was 24,619, about half the size of Tuesday's opening night crowd of 48,857.
- Cleveland 2B Jason Kipnis celebrated his 26th birthday.