Picotamide (G 137), a new non prostanoid inhibitor of in vitro arachidonic acid induced platelet aggregation, has been further characterized in in vitro and ex vivo studies. When whole blood was activated with collagen in the presence of picotamide 5 x 10(-4) M, thromboxane B2 production was decreased, and 6-keto-PGF1 alpha generation was significantly increased, suggesting a reorientation of platelet endoperoxide metabolism following blockade of thromboxane synthetase. Picotamide also inhibited platelet aggregation and clot retraction induced by the endoperoxide analogue U46619 in human platelets, indicating thromboxane A2-receptor antagonism, possibly of competitive nature. A single oral dose of picotamide 1 g in 24 healthy volunteers produced a significant inhibition of collagen, arachidonic acid and U46619-induced platelet aggregation. Serum levels of thromboxane B2 were also reduced. Chronic administration of picotamide 1.2 g/d to patients with vascular disease resulted in a prompt and persistent fall in their increased plasma levels of beta-thromboglobulin. The results indicate that picotamide is a combined thromboxane B2-synthetase inhibitor and thromboxane A2-receptor antagonist in human platelets, and that it may prove useful as an antithrombotic agent.