SEATTLE (AP) - Rich Harden lost to the Seattle Mariners - and the law of averages.

The Oakland A's right-hander gave up four runs in 5 2-3 innings and the A's fell 4-2 Tuesday night, ending his remarkable mastery over the Mariners at Safeco Field.

The four runs were the most ever scored against Harden (2-2) in a game at Safeco. He entered with a 5-0 record and 0.86 ERA in six career starts at Seattle's home. Overall in his nine appearances at Safeco, he had given up a combined four runs.

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``I thought he pitched similar to how he's pitched almost every time. He made two mistakes and cost him four runs,' Athletics manager Bob Melvin said.

The mistakes resulted in Mike Carp's two-run double in the first inning and Casper Wells' two-run homer in the sixth.

Yet it was a seemingly innocent infield single by Brendan Ryan in the first inning that drew the most attention.

The play began when Ryan reached on a one-out grounder to deep short. As he walked back to first base, Ryan noticed second base completely uncovered so he took off and made it without a throw. He popped up immediately and noticed the same lax defense at third, sliding in safely again without a throw.

``On balls hit into the hole like that when the shortstop has to dive or backhand the ball, the second baseman often times is backing up first,' Ryan said. ``If you get past first and second basemen you have second base open so I looked for it.

``Then I got to second and it looked like the closest person to third was right next to me. If get past him, I got third. It would have been fun to crawl home and score on that,' he said. ``It was really a wacky opportunity that presented itself.'

Said Harden: ``I don't think I've really seen anything like that. It's kind of embarrassing.

``You've got to put it behind you and go after the next hitter. It was a surprise how the game started. He was a heads-up baserunner. It caught everybody by surprise there and it changed the inning.'

Dustin Ackley then walked and Carp followed with a two-run double off the left-field wall.

``You see a guy take one bag on them being lackadaisical then to take two bags on one play, it's pretty amazing,' Carp said. ``It definitely fired us up.'

Wells, who came to Seattle in a four-player trade with Detroit on Saturday, said, ``I didn't know what was going on. It was like back in Little League or a Bad News Bears kind of play.'

Melvin said Ryan's play was ``not a lack of hustle or focus, it was just a lack of communication between them (infielders).'

``I don't think it affected us going forward. We got past it,' he said. ``We kept battling on their guy and finally got him out of the game.'

A's shortstop Eric Sogard said both he and third baseman Scott Sizemore broke toward second when they saw Ryan heading that way.

``We didn't even think about third and sure enough he's headed there and no one's there,' he said. ``It was unfortunate there and they ended up scoring. Something we'll learn from and it definitely won't happen again.'

The A's found themselves down 4-0 after Wells' shot in the sixth. Sizemore hit his fifth homer, a two-run drive in the seventh that chased Felix Hernandez (10-9).

That brought the A's within two and they loaded the bases with one out in the eighth. But Jeff Gray struck out Kurt Suzuki and Sogard.

Brandon League finished the ninth for his 25th save in 29 opportunities.

Hernandez improved to 12-4 with a 2.54 ERA in 21 career starts against Oakland, including five consecutive winning decisions. He hasn't lost to the A's since Sept. 19, 2008.

Hideki Matsui had another strong game, collecting three of the A's seven hits. He now has an 11-game hit streak, batting .533 (24 of 45) with 10 runs, six doubles, two home runs and 10 RBI. He has raised his batting average 49 points, to .264, since the All-Star break.

``He's been known to be a second-half guy but the streak that he is on is remarkable,' Melvin said. ``You just don't move your average like that.'

NOTES: Mariners 1B Justin Smoak took a hard ground ball to his left thumb in the sixth and had to leave the game. X-rays were negative. He is day to day. ... The Mariners promoted RHP Tom Wilhelmsen from Double-A Jackson. ... A's SS Cliff Pennington came out of Monday's game in the sixth inning with an outbreak of Bell's Palsy, a disorder of the nerve that controls movement of the face muscles. Medication has controlled the condition and he may be available again Friday at Tampa Bay. ... Seattle LHP Charlie Furbush, acquired from Detroit on Saturday, makes his third big league start Wednesday afternoon. He made a pair of July starts for the Tigers, combining for 7 1-3 innings, allowing 12 runs, eight earned. ... LHP Gio Gonzalez takes the mound for the A's on Wednesday. Gonzalez is 5-1 with a 3.14 ERA in 10 career appearances against Seattle.