Sulfinpyrazone added to PRP inhibited the release of serotonin induced by collagen. The inhibitory effect depended strongly on the strength of the collagen stimulus. Serotonin release was also inhibited (up to 73%) in PRP prepared from subjects who had ingested the drug. This is the first demonstration of a direct effect of a sulfinpyrazone in vivo on in vitro tests of platelet function. Prostaglandin synthesis was studied with lysates of washed platelets, arachidonic acid-14C, and silicic acid chromatography to isolate a reaction product which was tentatively identified as thromboxane B2. Platelet prostaglandin synthesis was shown to be strongly inhibited by sulfinpyrazone. Inhibition was competitive with respect to substrate. It is proposed that effects of sulfinpyrazone on platelet function may be due to inhibition of prostaglandin synthesis. The competitive nature of sulfinpyrazone inhibition may explain why sulfinpyrazone is a strong inhibitor of the release reaction under conditions of dilute collagent stimulation but is weak in the presence of stronger stimuli. In comparing the potency of inhibitors of platelet prostaglandin synthesis the nature of inhibition must be considered. Competitive inhibitors may be incorrectly regarded as weak if studied only at high substrate concentration.