1 The effects of the thromboxane synthetase inhibitor dazoxiben (UK 37248) on arachidonic acid and collagen-induced platelet aggregation and arachidonate acid metabolism were studied both in vitro and ex vivo in the presence and absence of sources of prostaglandin I2 synthetase. 2 In platelets activated by exogenous arachidonic acid, the anti-aggregatory activity of dazoxiben was weak compared with indomethacin, despite comparable inhibition of TXB2 production. This was due to the accumulation of pro-aggregatory metabolites, principally endoperoxides. 3 The anti-aggregatory activity of dazoxiben, both in vitro and ex vivo, was higher and more consistent when platelets were stimulated by collagen, threshold levels of which resulted in an endoperoxide accumulation only 2-3% of that achieved with exogenous arachidonic acid. 4 The anti-aggregatory activity of dazoxiben is enhanced if drug equilibration is facilitated by prolonging the preincubation time from 2 to 15 minutes. 5 Incubation of platelets with pig aortic microsomes, which act both as aggregant and a source of PGI2 synthetase, facilitates the conversion to PGI2 of some endoperoxides accumulated after dazoxiben, resulting in augmented anti-aggregatory activity. 6 Leukocytes as well as blood vessels have the capacity to generate PGI2 from platelet derived endoperoxides. This was demonstrated by the increases in 6-keto-PGF1 alpha accompanying decreased TXB2 production in clotted whole blood from volunteers treated with dazoxiben. 7 It was concluded that a closer approach to in vivo conditions allowing a fuller expression of the mechanism of action of dazoxiben could be achieved in vitro by stimulating platelets with a pathophysiological activator such as collagen in the presence of a source of PGI2 synthetase.