The interference of sodium salicylate with the effects of acetylsalicylic acid (ASA, aspirin) and indomethacin on arachidonic acid-induced platelet aggregation and thromboxane formation was studied in human platelet rich plasma. ASA and indomethacin suppressed both aggregation and the concomitant formation of thromboxane B2 whereas sodium salicylate alone had no significant effect on these parameters of platelet function. It did, however, partially prevent the inhibitory effects of ASA and indomethacin on platelet aggregation when it was added to platelet rich plasma before ASA or indomethacin. The inhibition of thromboxane formation by indomethacin was also prevented by sodium salicylate. When sodium salicylate was added to platelet rich plasma after ASA or indomethacin it did not modify the effects of these drugs. The present study indicates that sodium salicylate interferes with the effects of ASA and indomethacin on human platelet cyclo-oxygenase in vitro.