Wimbledon champion Venus Williams crashed out of the Charleston WTA clay-court tournament, losing 6-4, 7-6 (7/5) to German 16th seed Sabine Lisicki.
Second seed Williams, who was the champion in Charleston in 2004, on Thursday sent down five double faults and showed the same weaknesses in her game that were obvious in her three-set struggle against India's Sania Mirza in Wednesday's second round.
Defeat meant Venus was unable to keep the title in the family after sister Serena won in Charleston in 2008. Serena had been due to compete, but withdrew citing the leg injury she sustained in Miami last month.
Lisicki will tackle Russia's Elena Vesnina in the quarter-finals after she defeated Viktoria Kutuzova of Ukraine 7-7 (7/4), 7-5.
"It's a great victory beating Venus Williams. She's just a great champion. I still can't really believe I won," said Lisicki.
"It's one of my biggest wins. I think my win against Lindsay Davenport was really big as well, representing my country and beating her in my very first Fed Cup experience.