1. The pathways contributing to the platelet adhesion/aggregation reaction elicited by collagen microfibrils, administered to cats in vivo, were analysed. 2. The intra-aortic infusion of collagen (100 micrograms kg-1 in 1 min) caused an extensive activation of platelets, as evidenced by the time-dependent drop of free platelet numbers in whole blood, and the increases of 5-hydroxyindoles (5-HI), 5-hydroxytryptamine (5-HT) and thromboxane B2 (TXB2) levels in plasma, prepared from effluent venous blood sampled from the inferior caval vein. 3. 5-HT2 receptor blockade with ketanserin (0.63 mg kg-1 i.v., 10 min) and cyclo-oxygenase inhibition with aspirin (10 mg kg-1 i.v., 10 min) slightly attenuated the peak reduction of free platelets in whole blood in response to collagen without affecting changes in plasma 5-HI. Aspirin, but not ketanserin, reduced the collagen-induced changes in plasma TXB2, prostaglandin E2 (PGE2) and 6K-PGF1 alpha. 4. Dual TXA2 synthetase inhibition/TXA2-prostaglandin endoperoxide receptor antagonism with ridogrel (5 mg kg-1 i.v., 10 min) halved the drop in free platelets, reduced the release of platelet 5-HI, inhibited the increase in plasma TXB2 and elevated that of 6K-PGF1 alpha and PGE2 in response to collagen. 5. Combined treatment with ketanserin and aspirin reduced the collagen-induced drop of free platelets and the release of platelet 5-HI to a similar extent as ridogrel alone; plasma prostanoids were affected as with aspirin alone. 6. Combined administration of ketanserin and ridogrel virtually eliminated the collagen-induced platelet adhesion/aggregation response and release of 5-HI; prostanoids were affected as with ridogrel alone. 6. Combined administration of ketanserin and ridogrel virtually eliminated the collagen-induced platelet adhesion/aggregation response and release of 5-HI; prostanoids were affected as with ridogrel alone. 7. The results indicate that the interplay between 5-HT and arachidonic acid metabolites is causally involved in the platelet reaction to activation induced by collagen in cats in vivo.