Resistance to activated protein C (APC resistance) was measured in 284 individuals (169 females, 115 males) with a history of objectively confirmed venous thrombosis and/or pulmonary embolism. A decreased APC resistance ratio was found in 75 patients (26%), 47 were females, 28 males. Factor V Leiden was investigated in 60 of 75 patients with APC resistance, of whom 46 were heterozygous, 4 homozygous. In 10 APC resistant patients the Arg 506 Glu mutation was not identified. The median age of the first thromboembolic event in patients with APC resistance was 42 years (range 15-82 years). Most patients had a history of deep vein thrombosis (83%), 28% had experienced pulmonary embolism. More unusual sites of thrombosis were the deep arm veins (7%) and mesenteric veins (one patient, 1.3%). 53% of patients developed the first thromboembolic event spontaneously. Precipitating conditions for thromboembolism were surgery in 9.3% and trauma in 8%. In one third of female patients the first thromboembolic event occurred in conjunction with pregnancy and delivery (14.8%) or oral contraceptives (19%). At the time of investigation 40% of patients with APC resistance had experienced recurrent thromboembolic events. The family history was positive in 60% of patients. We conclude that the clinical feature of APC resistance is similar to the feature of a deficiency of antithrombin, protein C and protein S. Pregnancy, delivery and oral contraceptives seem to be a relevant additional risk factors for thrombosis in females with APC resistance.