Valentino Rossi crashed out at turn two after contact with Jorge Lorenzo, forcing Ben Spies through the gravel in the process.
Casey Stoner ran through the gravel while leading on lap 5, dropping him to seventh.
Andrea Dovizioso, Marco Simoncelli and Cal Crutchlow were all given ride-through penalties for jumping the start.
MotoGP rookie Karel Abraham withdrew from the race due to concentration problems caused by the head impact he suffered at Aragon on September 18.
Honda test riders Shinichi Ito and Kosuke Akiyoshi have got wild-card rides for their home round, while Damian Cudlin is making his MotoGP debut as a replacement for the injured Loris Capirossi.
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1. Dani Pedrosa
ESP Repsol Honda 42m 47.481s
2. Jorge Lorenzo
ESP Yamaha Factory Racing 42m 54.780s
3. Casey Stoner
AUS Repsol Honda 43m 5.861s
4. Marco Simoncelli
ITA San Carlo Honda Gresini 43m 11.031s
5. Andrea Dovizioso
ITA Repsol Honda 43m 11.172s
6. Ben Spies
USA Yamaha Factory Racing 43m 25.085s
7. Nicky Hayden
USA Ducati Marlboro 43m 26.468s
8. Colin Edwards
USA Monster Yamaha Tech 3 43m 32.504s
9. Hiroshi Aoyama
JPN San Carlo Honda Gresini 43m 36.555s
10. Randy de Puniet
FRA Pramac Racing 43m 46.503s
11. Cal Crutchlow
GBR Monster Yamaha Tech 3 44m 1.445s
12. Kousuke Akiyoshi
JPN LCR Honda 44m 9.190s
13. Shinichi Ito
JPN Honda Racing Team 44m 13.862s
ESP LCR Honda
15. Alvaro Bautista
ESP Rizla Suzuki
AUS Pramac Racing
ESP Mapfre Aspar
ITA Ducati Marlboro
CZE Cardion AB Motoracing