In 29 patients (17 females) homozygous Arg 506 Gln mutation (FV Leiden) was identified. 25 had been investigated because of venous thromboembolism (VTE); four asymptomatic patients were found during family studies. The first VTE had occurred significantly earlier in females (median age [m] 26 years, range 17–49) than in males (m=38 years, range 21–82) (P = 0.01). 12 females (80%) had taken oral contraceptives (OC, oestrogen content 0.02–0.1 mg) for 6–150 months prior to thrombosis. Further triggering conditions in females were hormone replacement (n = 1) and pregnancy (n = 2). In 8/10 males the first VTE had occurred spontaneously — in two after surgery. The sites of VTE were deep vein thrombosis, pulmonary embolism, caval vein thrombosis and superficial thrombophlebitis. From our data we conclude that OC medication is the most important precipitating factor for VTE in females with homozygous FV Leiden.