Paris - US hopes at the French Open were extinguished on Thursday as marathon man John Isner was once again involved in an epic duel, the fourth longest in Grand Slam history, which he lost this time.
The giant Isner found himself as the last American standing out of eight starters after qualifier Jesse Levine had earlier gone down 6-4, 7-5, 6-2 to Milos Raonic of Canada.
But after what turned out to be, at five hours 41 minutes, the second longest match in French Open history and the fourth longest in Grand Slam history, Isner lost 7-6 (7/2), 4-6, 4-6, 6-3, 16-18 to French wildcard Paul-Henri Mathieu.
Mathieu finally entered the third round by converting his seventh match point, as Isner hit a forehand wide.
The American hit 41 aces, but had 98 unforced errors.
Ironically it was against another Frenchman, Nicolas Mahut, that Isner played the longest match in history at Wimbledon in 2010 when he took 11 hours and five minutes, spread over three days, to win 6-4, 3-6, 6-7 (7/9), 7-6 (7/3), 70-68.
The loss means that the American drought in Grand Slam titles moves on to 34 since Andy Roddick won the 2003 US Open.
The last American winner in the French Open was Andre Agassi in 1999 and he was also the last American to reach the quarter-finals here four years later.
The win for the 30-year-old Mathieu came after he spent 15 months out of the game with a serious injury to his left knee that required extensive surgery.
He only returned to action early this year and his ranking had fallen so low he needed a wildcard to get into the main draw at Roland Garros.
Results from the fifth day of the 2012 French Open at Roland Garros on Thursday (x denotes seeded player):
Fabio Fognini (ITA) bt Viktor Troicki (SRB x28) 6-2, 3-6, 4-6, 6-3, 8-6
Jo-Wilfried Tsonga (FRA x5) bt Cedrik-Marcel Stebe (GER) 6-2, 4-6, 6-2, 6-1
David Goffin (BEL) bt Arnaud Clement (FRA) 3-6, 7-6 (7/2), 0-6, 6-2, 6-1
David Ferrer (ESP x6) bt Benot Paire (FRA) 6-3, 6-3, 6-2
Mikhail Youzhny (RUS x27) bt Robin Haase (NED) 6-3, 7-6 (7/5), 6-4
Paul-Henri Mathieu (FRA) bt John Isner (USA x10) 6-7 (2/7), 6-4, 6-4, 3-6, 18-16
Tommy Haas (GER) bt Sergiy Stakhovsky (UKR) 6-2, 6-3, 6-2
Santiago Giraldo (COL) bt Bernard Tomic (AUS x25) 6-4, 6-1, 6-3
Andy Murray (GBR x4) bt Jarkko Nieminen (FIN) 1-6, 6-4, 6-1, 6-2
Janko Tipsarevic (SRB x8) bt Jrmy Chardy (FRA) 7-6 (7/4), 6-1, 7-5
Julien Benneteau (FRA x29) bt Dmitry Tursunov (RUS) 6-4, 6-4, 6-4
Leonardo Mayer (ARG) bt Philipp Kohlschreiber (GER x24) 7-6 (7/5), 7-6 (7/4), 7-5
Nicolas Almagro (ESP x12) bt Marcos Baghdatis (CYP) 6-4, 6-3, 7-5
Juan Monaco (ARG x13) bt Lukas Rosol (CZE) 7-6 (7/4), 6-0, 7-6 (7/5)
Milos Raonic (CAN x19) bt Jesse Levine (USA) 6-4, 7-5, 6-2
Eduardo Schwank (ARG) bt Florian Mayer (GER x32) 2-6, 6-3, 6-4, 7-6 (7/4)
Rafael Nadal (ESP x2) bt Denis Istomin (UZB) 6-2, 6-2, 6-0
Suspended due to darkness:
Marcel Granollers (ESP x20) level with Malek Jaziri (TUN) 7-6 (7/1), 3-6, 6-1, 3-6
Angelique Kerber (GER x10) bt Olga Govortsova (BLR) 6-3, 6-2
Li Na (CHN x7) bt Stphanie Foretz (FRA) 6-0, 6-2
Christina McHale (USA) bt Lauren Davis (USA) 6-1, 6-3
Yaroslava Shvedova (KAZ) bt Sofia Arvidsson (SWE) 6-1, 6-0
Carla Surez (ESP) bt Sesil Karatantcheva (KAZ) 4-6, 6-4, 6-1
Francesca Schiavone (ITA x14) bt Tsvetana Pironkova (BUL) 2-6, 6-3, 6-1
Varvara Lepchenko (USA) bt Jelena Jankovic (SRB x19) 7-6 (7/4), 4-6, 6-4
Nina Bratchikova (RUS) bt Claire Feuerstein (FRA) 3-6, 6-3, 7-5
Petra Kvitova (CZE x4) bt Urszula Radwanska (POL) 6-1, 6-3
Arantxa Rus (NED) bt Virginie Razzano (FRA) 6-3, 7-6 (7/3)
Julia Grges (GER x25) bt Heather Watson (GBR) 6-3, 6-4
Kaia Kanepi (EST x23) bt Irina Begu (ROM) 6-4, 6-1
Caroline Wozniacki (DEN x9) bt Jarmila Gajdosova (AUS) 6-1, 6-4
Klara Zakopalova (CZE) bt Maria Kirilenko (RUS x16) 6-4, 3-6, 6-3
Anastasia Pavlyuchenkova (RUS x22) bt Melinda Czink (HUN) 4-6, 6-3, 6-3
Peng Shuai (CHN x28) bt Lourdes Domnguez (ESP) 6-4, 6-3
Postponed until Friday:
Maria Sharapova (RUS x2) v Ayumi Morita (JPN)