1. Exposure of human and rabbit blood platelets to all full agonists tested induces agonist-specific (or homologous) desensitisation except in the case of adrenaline and collagen in human platelets. 2. Desensitisation to vasopressin and 5-hydroxytryptamine (5HT) develops rapidly and results from suppression of maximal responsiveness without significant shift in the dose/response curve (Type I). In rabbit platelets, maintenance of desensitisation to 5HT is correlated with the extracellular 5HT concentration. Responsiveness to other agonists is either unaffected, or is enhanced due to a shift in the dose/response curve to the left without change in maximal responsiveness. 3. Homologous desensitisation to ADP, U-46619 and thrombin develops more slowly, is correlated with disaggregation and is associated with a shift in the dose/response curve to the right without suppression of maximal responsiveness (Type II). Responsiveness to most other agonists is either unaffected, or is enhanced due to a shift in the dose/response curve to the left without a change in maximal responsiveness. However, exposure to thrombin suppresses the maximal response to vasopressin without a shift in the dose/response curve, and exposure to U-46619 causes a shift in the dose/response curve for collagen to the right. 4. In human platelets prolonged exposure to 5HT causes agonist non-specific (or heterologous) desensitisation in which responsiveness to all agonists except adrenaline is suppressed as a result of shifts in the dose/response curves to the right. 5. We propose that Types I and II homologous desensitisation result respectively from prolonged receptor occupancy and from either activation of degradative mechanisms for the agonist or processing of the receptor to a lower affinity state.