The prophylaxis of venous thromboembolism after operation has increased the interest in the administration of drugs which depress in‐vitro platelet function. An animal model was designed to test some of these drugs, utilizing a free‐flowing venous system in which intimal damage and platelet deposition at an electrode were primary events. Heparin, in generally recognised therapeutic doses, was the most effective drug tested; lesser doses still had a significant though diminished effect. Acetyl salicylic acid in three‐dose schedules was most effective at high plasma concentrations. Likewise, higher doses of dipyridamole were effective in preventing thrombus formation. It was interesting to note a synergistic effect of a combination of low doses of acetyl salicylic acid and dipyridamole when each agent used alone had a minor thromboprophylactic effect. High molecular weight dextran had more effect in higher doses, but at the expense of a marked prolongation of the bleeding time. The results of these animal experiments are discussed with reference to recent clinical trials of similar agents. Possible alternative mechanisms are suggested to produce the same effect as heparin in subtherapeutic