Venus was broken seven times by Kleybanova
World number three Venus Williams was knocked out of the Madrid Open at the second-round stage by unseeded Russian teenager Alisa Kleybanova.
Williams was broken seven times by the 19-year-old world number 26 and eventually went down 6-3 3-6 7-5.
Fourth seed Jelena Jankovic reached the third round after seeing off Slovakia's Daniela Hantuchova 7-5 6-2.
British number one Anne Keothavong was beaten 6-1 7-5 by Lucie Safarova of the Czech Republic.
Keothavong managed to save three break points in the first set but was still swept aside by the world number 50.
She made her opponent work harder in the second, but Safarova won to book a third-round meeting with either top seed Dinara Safina or Na Li.
The biggest shock of the day was Williams' defeat at the hands of Kleybanova.
"I felt like she won by just being aggressive from both sides of the court," said Williams, who joined her sister Serena in making an early exit in Madrid.
"Against me she had to go for everything and make everything. All her balls landed in today."
Kleybanova will next face Danish ninth seed Caroline Wozniacki, who had little trouble in seeing off American Varvara Lepchenko 6-3 6-1.
Unseeded former world number one Amelie Mauresmo of France overwhelmed China's 15th seed Jie Zheng 6-2 7-5 and next plays Russian third seed Elena Dementieva.
Other second-round winners included Italy's Francesca Schiavone and Agnes Szavay of Hungary.
Schiavone eased to a 6-4 6-2 win against Czech Petra Kvitova, while Szavay fought back from a set down to beat Arvane Rezai of France 2-6 7-5 6-2.
Russia's Vera Dushevina also lost the first set against Italian Roberta Vinci but recovered to win 4-6 6-1 6-4.