Staphylococcus aureus Cowan I (Cowan Staph A+), which synthesizes protein A (Staph A), induced histamine release from human basophils. In contrast, S. aureus Wood 46 (Wood Staph A-), which does not synthetize Staph A, did not induce histamine secretion. Soluble Staph A and Cowan Staph A+ induced histamine release by interacting with the alternative F(ab')2-binding site of IgE and/or IgG present on human basophils. Pepstatin A, a pentapeptide synthetized by various actinomycetes, induced histamine secretion by activating a specific membrane receptor, which is also activated by synthetic formylmethionine-containing peptides.