In order to determine which drugs would be most effective as inhibitors of platelet release and aggregation, In vitro release reactions and platelet aggregometry were used to evaluate aspirin, dipyridamole, sulfinpyrazone, flurbiprofen, low molecular weight dextran (dextran 40), prostaglandin E, (PGE1), apyrase, and adenosine. Adenosine diphosphate-induced aggregation was most effectively inhibited by PGF1, sulfinpyrazone, and dipyridamole. The latter had to be used in large doses. Collagen and epinephrine-induced release and aggregation were inhibited by the same drugs as well as by aspirin and apyrase. Antithynocyte globulin (ATG)-lnduced release and aggregation could only be partially blocked by these agents. In vitro studies suggest that sulfinpyrazone is one of the most effective of platelet inhibitors currently available for clinical testing.