Abstract The action of thrombin, Reptilase, and a fibrinopeptide B-releasing enzyme from the Southern Copperhead snake venom on gel-filtered rabbit platelets has been studied. Of these enzymes, only thrombin aggregated the platelets. A mixture of Reptilase and the Southern Copperhead enzyme, which closely mimicked the enzymatic activity of thrombin on fibrinogen, failed to induce aggregation. These results indicate that thrombin does not aggregate platelets by its action on fibrinogen on the platelet surface. Incubation of the gel-filtered platelets with the snake venom enzymes modified the platelet aggregation response to ADP. The rates of both aggregation and disaggregation were moderately decreased after incubation with Reptilase, and the rate of disaggregation was decreased after incubation with the Southern Copperhead enzyme.