We analysed a cohort of heterosexual HIV- serodiscordant couples with the aim of evaluating the risk of transmission ascribed to unprotected orogenital intercourse. A total of 135 seronegative individuals (110 women and 25 men), whose only risk exposure to HIV was unprotected orogenital sex with their infected partner, registered 210 person-years of follow-up. After an estimated total of over 19,000 unprotected orogenital exposures with the infected partner not a single HIV seroconversion occurred.