The biologic activity of the anaphylatoxic peptides C5a and C3a is regulated efficiently at the target-cell level by the phenomenon of desensitization. Desensitization of platelets is stimulus specific and can be induced by low concentrations of anaphylatoxins without any preceding secretory event. In contrast to activation to secretion, desensitization is Ca++ independent but much more time consuming, especially at lower temperatures where both processes differ markedly in reaction velocity. This low zone desensitization insures that secretion from platelets only occurs when high amounts of anaphylatoxins are rapidly generated in the vicinity of the target-cell. Consequently, stimulus-specific unresponsiveness of the target cells can be induced by slowly increasing the concentration of the respective stimuli in their vicinity. Cellular control seems to act as a first-line mechanism of regulation, whereas the role of fluid-phase control is considered as preventing longer persistence and systemic accumulation of active anaphylatoxins.