Rabbit plasma kallikrein incubated with rabbit C5 resulted in the generation of chemotactic and secretagogue activity for rabbit neutrophils. This effect on C5 appeared to be due to kallikrein itself and not to a contaminating enzyme, because it could be inhibited by anti-kallikrein IgG or by soybean trypsin inhibitor to the same extent the kinin generation by the same kallikrein preparation was inhibited by these agents. The chemotactic response was consistent with the generation of a C5a-like peptide from C5 because the effect could be partially inhibited by carboxypeptidase N and was related to the generation of a small (approximately 14,000 mol wt) fragment of C5. No direct chemotactic response was detectable for kallikrein, activated Hageman factor, high-molecular weight kininogen, or intact C5. Incubation of Kallikrein, high-molecular weight kininogen, and Hageman factor together, so that activation of all three proteins occurred, did not results in the generation of detectable chemotactic activity.