Ajoene, the major antiplatelet compound derived from garlic, synergistically potentiates the antiaggregatory action of prostacyclin, forskolin, indomethacin and dypiridamole. For collagen-induced platelet aggregation in human PRP, the ID50 for ajoene is 95 +/- 5 microM. However, in the presence of the antiaggregatory drugs mentioned above, the ID50 for ajoene decreases more than what would be predicted on the basis of simple additive effects. Similarly, the ID50 for prostacyclin decreases from 1 nM to 0.15 nM in the presence of 80 microM ajoene. Isobolic curves for the various combinations of ajoene with prostacyclin or indomethacin exhibit departure from linearity, as predicted for a potentiated synergism between ajoene and these drugs. Dypiridamole, which in PRP has very little effect on the dose-response curve for ajoene, when assayed in whole blood decreases the ID50 for ajoene by a factor of four. These results demonstrate that the antithrombotic potential of ajoene is substantially increased in the presence of physiologically and pharmacologically active antiplatelet agents.