||Group B streptococcus (GBS) infections are often associated with a poor acute cellular response. Previous studies showed that GBS inactivate the complement-derived chemotactic activity in human zymosan-activated serum for human polymorphonuclear leukocytes (PMNs). Most strains of GBS were found to possess this ability to inactivate C5a and C5adesarg, the major complement-derived chemoattractants, and this enzymatic activity was termed C5a-ase. Subsequent studies showed that GBS C5a-ase executes this inhibitory activity by cleavage of a hep tapep tide from the carboxy terminus of C5a and the C5a-ase has been purified to homogeneity. The present studies investigated the ability of the GBS C5a-ase to inactivate the C5a chemoattractants of different animal species in vitro, including human, monkey, rat, rabbit, sheep, guinea pig and cow. Animal C5a was partially purified from zymosan-activated serum by 1 N HC1 precipitation and in some cases, further purification was achieved by gel-filtration on Sephadex G-75. The ability of GBS to inactivate the partially purified C5a was assessed in vitro using human PMN adherence and chemotaxis as indicators of C5a activity. Human, monkey and bovine C5a as well as recombinant human C5a (rhC5a) were inactivated by C5a-ase containing strains of GBS. In contrast, C5a prepared from rat, rabbit, sheep, and guinea pig appeared to retain full chemotactic activity for human PMNs after exposure to C5a-ase containing GBS. We also found that GBS did not inactivate rat or sheep C5a chemotactic activity when chemotaxis was assayed using rat or sheep PMNs, respectively. Finally, we showed that PMN accumulation in rat skin in vivo to rat C5a was not affected by treatment with GBS. These data suggest that GBS C5a-ase exhibits species specificity in its ability to inactivate C5a. This species specificity will restrict the choice of animal models for testing the virulence of C5a-ase-negative mutant of GBS.