Oral administration of 100 or 200 mg suloctidil to healthy volunteers resulted in serum thromboxane B2 (TxB2) inhibition. This reached a maximum level between 90 min and 4 h after drug ingestion. TxB2 levels returned to 75% of basal values 6 h after 100 mg and more than 8 h after 200 mg, reaching control values at 24 h. Different experiments were performed to define the metabolic step at which suloctidil acts to inhibit serum TxB2 generation. Suloctidil prevented TxB2 synthesis also when platelet-rich plasma was stimulated by exogenous arachidonic acid or whole blood was clotted in the presence of exogenous arachidonic acid. This rules out the possibility that it inhibits phospholipases. No rediversion of prostaglandin synthesis after suloctidil occurred concomitantly with TxB2 inhibition, suggesting that the drug is not a selective thromboxane synthase inhibitor. In contrast, a significant reduction of serum PGE2 formation was found, suggesting a mechanism of action of suloctidil involving inhibition of cyclo-oxygenase. This was supported by the finding that PGI2 production by rat smooth muscle cells stimulated with arachidonic acid was significantly prevented by suloctidil in vitro. Suloctidil, however, did not prevent aspirin-induced inhibition of serum TxB2 generation. Blockade of platelet cyclo-oxygenase activity by suloctidil is therefore exerted at a level different from that of aspirin. In conclusion, suloctidil is a relatively weak nonselective cyclo-oxygenase inhibitor whose effect on platelet TxA2 production hardly accounts for its reported inhibitory effect on platelet aggregation.