It is unclear what actually induces eosinophil degranulation in vivo. We examined eosinophil cationic protein (ECP) release from normal human eosinophils (Eos) in response to C3a and C5a. C3a and C5a induced remarkable ECP release when Eos were preincubated with cytochalasin B. ECP release induced by C3a or C5a was greater than that induced by PAF at a concentration of 10(-7) M. The ED50 for ECP release was 3 x 10(-8) M and 3 x 10(-9) M for C3a and C5a, respectively. C3a or C5a elicited a rapid and transient rise in [Ca2+]i. These results suggest that C3a and C5a may contribute to hypersensitivity diseases by inducing eosinophil degranulation.