The mechanism of platelet activation by thrombin was investigated using suspensions of human platelets. The assumption that the thrombin-platelet reaction shows characteristics of an agonist-receptor interaction was corroborated by an analysis of the relation between thrombin concentration and yield of 14C-serotonin secretion. However, silent thrombin binding sites that decrease the free thrombin concentration interfere with this interaction. When the influence of these binding sites is eliminated by a decrease in platelet concentration or by saturation with DIP-thrombin the concentration-response relationship can be interpreted by the adsorption isotherm of Langmuir. The binding sites interfering with the thrombin receptor interaction are identical with the high affinity binding sites of platelets. For the yield of secretion the velocity of thrombin addition is important. The platelet reaction decreases by slowing the rate of thrombin addition. In comparison with the reaction occurring at 37 degrees C, in that occurring at 0 degree C only the rate but not the yield of receptor stimulation is diminished. The results are in accordance with the assumption that the yield of platelet activation is determined by the equilibrium binding of thrombin. It is suggested that at 37 degrees C the processes of thrombin binding to the receptor, of receptor modification and of cellular response are immediately coupled with one another and that the rate-limiting step is the binding of thrombin to the receptor.