Johan Santana started off great — three perfect innings. The end result was all too familiar.

Michael Morse hit a grand slam, Bryce Harper also homered and the Washington Nationals became the latest team to tag a struggling Santana in their 6-4 victory over the New York Mets on Friday night.

Ross Detwiler tossed six solid innings and the Nationals sent Santana to his fifth loss in the last five starts.

"I felt pretty good," Santana said. "I was commanding my fastball better tonight. It came down to a couple pitches. The second time through, they made adjustments. I missed location."

Since throwing a career-high 134 pitches to finish off the first no-hitter in Mets history on June 1, Santana (6-9) has lost seven of 10 decisions. The 33-year-old left-hander, who missed last season following major shoulder surgery, permitted six runs and seven hits over five innings in his second outing since spending three weeks on the disabled list with a sprained ankle.

That period of rest was also intended to recharge his surgically repaired shoulder. But he lasted only 1 1-3 innings last Saturday against Atlanta, the worst start of his career, and couldn't slow down the Nationals, either.

Still, Mets manager Terry Collins was upbeat.

"His arm strength's back," Collins said. "Early in the game, his command was good. All of a sudden, left some balls in the middle of the plate and they hit 'em hard. You've got to hit your spots. (But) today's stuff was better than the last time out, the crispness of the fastball and the changeup.

"The thing he wanted to achieve this year was to go out there 30 times . and be ready 100 percent for spring training (in 2013), and we're on track for that. His velocity hopefully will increase as he gets some rest this winter. I think he's going to be back to where he was early in the year."

Handed a 2-0 lead, the two-time Cy Young Award winner was perfect through three innings. But the NL East leaders strung together four consecutive hits in the fourth, capped by Morse's 12th homer.

Harper, coming off a 3-for-32 road trip, turned on a fastball in the fifth for a two-run shot.

Santana is 0-5 with a 15.63 ERA in his past five starts, allowing at least six runs in each appearance. His ERA was 2.76 through June but now sits at 4.85.

"My season has been a roller-coaster — a lot of ups and downs, good days, bad days — but I'm very positive because I'm coming back from a major surgery," Santana said. "Being able to be out there every five days, it means a lot to me. This will be a good sign looking forward, being able to pitch without any problems in my arm. My shoulder's fine. The velocity's there, but I'm still putting things together with my mechanics and my legs. I feel like I'm making progress."

The Nationals, who have the best record in baseball, returned home following an 8-2 trip and have won 10 of 12 overall. Washington began the day four games ahead of second-place Atlanta.

Losers of five of seven, the Mets fell to 10-23 since the All-Star break and have dropped 10 of 13 to the Nationals this season.

Detwiler (7-5) allowed three runs and six hits with one strikeout and a walk.

Craig Stammen gave up a homer to Mets newcomer Kelly Shoppach leading off the seventh and Drew Storen worked the eighth. Tyler Clippard walked two in the ninth before earning his 26th save.

Santana gave up consecutive singles to Jayson Werth, Harper and Ryan Zimmerman in the fourth, loading the bases for Morse. The cleanup man launched a 1-1 fastball the opposite way to right-center for a 4-2 Nationals lead, extending his hitting streak to 13 games.

Werth kept the fifth inning alive with a two-out single and the 19-year-old Harper sent a shot to right-center for his 11th home run.

"We tried to come up and in to Morse and it just stayed up pretty much in the middle of the plate," Santana said. "I was supposed to throw a fastball away to Harper and it just came back in there. That's telling me I have to work on my command. But compared to my last (start), I felt this one was way better."

After getting two quick outs in the first, Detwiler gave up three consecutive hits, including one of three doubles by Scott Hairston and a two-run single by Daniel Murphy.

Detwiler then walked Ronny Cedeno, but avoided further damage and allowed only one run and three hits over his final five innings. In three starts this season against the Mets, the lefty is 2-0 with 1.50 ERA.

Cedeno's RBI groundout in the sixth scored Hairston.

Zimmerman shined defensively early with three sparkling plays on hard-hit grounders. The third baseman later started a key 5-4-3 double play in the eighth with the potential tying run at the plate.

Before the game, the Nationals activated All-Star shortstop Ian Desmond from the 15-day disabled list. With his return from a 25-game absence due to an oblique strain and other core members missing time this season with injuries, the Nationals had Desmond, Werth, Harper, Zimmerman, Morse and Adam LaRoche in the lineup together for the first time.

NOTES: Desmond finished 0 for 4. To make room for him, the Nationals designated veteran infielder Cesar Izturis for assignment. ... Hairston's three doubles matched a team record. ... Including the series opener, Washington plays 27 of its final 44 games at home, more than any team in the majors during the remainder of the season. ... Saturday's pitching matchup pits left-hander Jonathon Niese against Washington RHP Edwin Jackson.