Yamaha's championship leader Maverick Vinales led the way by more than half-a-second in first practice for the Austin MotoGP round.
After winning his opening two races with Yamaha, in Qatar and Argentina, Vinales has set his sights on becoming the first rider other than Marc Marquez to win at the Circuit of the Americas.
Marquez led the way after the first block of running, with a 2m05.535s lap, with Honda stablemates Cal Crutchlow - before a crash at Turn 6 - and Dani Pedrosa having also spent time at the top.
The Spaniard was 0.574 seconds clear of Pedrosa until he was pipped by Vinales, who turned a 2m05.462s with 15 minutes to go.
That put Vinales 0.073s ahead of Marquez, and he then set a 2m04.923s the next time around to go 0.612s clear.
Marquez improved again before the session was out, but only by less than a tenth, and Vinales finished with an advantage of 0.577s.
Ducati had a quiet session until the final five minutes, when Andrea Dovizioso jumped up from 12th to third, and Jorge Lorenzo from 16th to sixth.
Vinales' team-mate Valentino Rossi also climbed up the order from outside the top 10 in the closing stages, on soft tyres, and finished eighth.
Tech3 Yamaha's Johann Zarco was the best of the rookies in fourth, while Alvaro Bautista pipped Lorenzo after the chequered flag to take fifth on his 2016-model Aspar Ducati, the last of the riders within a second of Vinales.
Pedrosa wound up seventh ahead of Rossi, while Aprilia's Aleix Espargaro and Pramac Ducati's Danilo Petrucci completed the top 10 and Crutchlow slipped to 11th despite rejoining on his second LCR Honda.
Andrea Iannone tried Suzuki's winglet-replacement front fairing but finished the session down in 16th place, 1.901s off the pace, four spots ahead of rookie team-mate Alex Rins.
Pol Espargaro was the best of the KTMs in 21st place, after saving a wild moment under braking at Turn 12 inside the final 10 minutes.