Newport - US top seed John Isner crashed out on Tuesday in the opening round of the ATP Hall of Fame Championships, losing to 161st-ranked countryman Rajeev Ram 6-7 (5/7), 6-3, 7-6 (10/8).
Isner, ranked 18th, was coming off a third-round Wimbledon exit at the hands of reigning US Open champion Marin Cilic after dropping the fifth set 12-10. He was seeking a third title at Newport and the 10th ATP crown of his career.
Isner blasted 21 aces with only a lone double fault but Ram fired 18 aces back and rallied after dropping the first-set tie-breaker, taking the only break of the second set and outlasting the top American after neither broke in the last.
Ram, whose only career ATP title came at Newport in 2009, advanced to a second-round matchup against Japan's 144th-ranked Yuichi Sugita, a first-round Wimbledon loser who ousted American Ryan Harrison 6-1, 5-7, 6-3.
Also defeated was US eighth seed Tim Smyczek, who fell 6-3, 6-4 to Czech Jan Hernych.
Two other US seeds advanced with number four Jack Sock dumping Czech Radek Stepanek 6-2, 6-0 and number six Sam Querrey dispatching Australian Matthew Ebden 7-6 (7/3), 7-6 (7/1).
Next up for Sock will be Slovakia's Lukas Lacko, who defeated Belgium's Niels Desein 6-3, 3-6, 6-2. Querrey's second-round foe will be German Dustin Brown, who beat Swiss Adrien Bossel 7-6 (7/4), 6-3.
Tunisia's Malek Jaziri downed Ante Pavic 6-2, 4-6, 7-5 to set a second-round date with another Croatian opponent - second seed Ivo Karlovic, the highest-ranked remaining player at 24th in the world.
Rain hit before the start of the final first-round match between French fifth seed Adrian Mannarino and German wildcard Tommy Haas, leaving France's Edouard Roger-Vasselin to await the winner after eliminating Slovenia's Blaz Kavcic 4-6, 6-3, 6-2.