There is evidence from clinical studies and animal experiments that aspirin has a greater antithrombotic activity in males compared to females. We investigated platelet function in vitro and in vivo in rabbits before and after the administration of a dose of aspirin (5 mg/kg) which inhibited collagen stimulated thromboxane B2 generation. Infusion of collagen into untreated animals resulted in a 38 +/- 4% (m +/- SE, n = 13) decrease in platelet count (assessed by whole blood radioactivity) in the male animals, and a 27 +/- 3% (m +/- SE, n = 13) in the female animals. Pretreatment with aspirin resulted in a significant inhibitory effect in the male but not the female animals (p less than 0.05). The male animals had significantly greater thromboxane B2 generation in vivo than did the female animals following an equal dose of collagen (males, 2.64 +/- 0.7 ng/ml thromboxane B2, n = 14; females, 1.67 +/- 0.4 ng/ml thromboxane B2, n = 15, p less than 0.05). In contrast no sex related difference in the inhibitory effect of aspirin on maximal collagen induced aggregation was found when platelets were studied in vitro. The greater reactivity of male patients in vivo may be accounted for by the observed increase in thromboxane B2 generation. This might also explain the greater thrombotic tendency of males, and the observed difference in the antithrombotic effect of aspirin in males and females.