Marquez's problem was a crash at Lukey Heights early in the session.
The Honda rider quickly got up unhurt, but could not improve on sixth place when he rejoined the session.
His team-mate Pedrosa had just split an initial Yamaha one-two to take second behind Lorenzo when he had to pull off at the second corner with a mechanical problem in the closing minutes.
Meanwhile Lorenzo had a serene session on his Yamaha, lapping ever faster until a 1m28.961s put him half a second ahead.
Gresini Honda's Alvaro Bautista also crashed but got going again to grab second on his last run.
Pedrosa retained third, ahead of the Yamahas of Valentino Rossi and Cal Crutchlow.
Randy de Puniet was again top CRT rider in a very impressive eighth place, ahead of all the Ducatis and nearly a second faster than Aspar team-mate Aleix Espargaro.
Hector Barbera also had an accident. He was unhurt.
The injured Stefan Bradl was ruled out of the session after assessing his condition in practice one.