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A group of 100 consecutive patients treated for deep vein thrombosis in the Trnovo Hospital of Internal Medicine from January 1992 to December 1994, was studied for the presence of a new type of thrombophilia – resistance to activated protein C. There were 40 women and 60 men, aged 16 to 60 years ( = 39). Primary deep vein thrombosis was established in 38 patients (18% women, 82% men), and sec­ondary deep vein thrombosis in 62 patients (53% women, 74% men). Thirty-two per cent of patients had a positive family history; 79 per cent were treated for the first episode of deep vein thrombosis and the remainder for recurrent episodes. Resistance to activated protein C was determinated using a ratio between acti­vated partial thromboplastin time with purified activated protein C and activated partial throm­boplastin time without activated protein C. The lower normal limit was determined by measur­ing the activated protein C ratio in 100 sex and age matched healthy subjects ( ± 2 SD). Subjects with an activated protein C ratio less than 2,0 were considered resistant to activated protein C. Twenty patients were exclud­ed from the study because of anticoagulant treatment, and 9 because of the presence of lupus anticoagulants. Activated protein C resis­tance was established in 10 (14%) of the remain­ing 71 patients (6 women and 4 men). In the con­trol group, the prevalence of activated protein C resistance was 3 per cent (3 men) (p < 0,05). One patient showed antithrombin III deficiency, and 2 patients protein C deficiency, but none of them had activated protein C resistance. There were no association between activated protein C resistance and primary or secondary deep vein thrombosis, positive family history and first or recurrent episodes of the disease. The results of the study indicate that activated protein C resistance is a frequent independent risk factor for deep vein thrombosis.