Protein A from Staphylococcus aureus (Staph A) induces histamine secretion from human basophil leucocytes in the concentration range 10(-4) - 10 micrograms/ml. This reaction has great similarities to that of antigen or anti-IgE-induced release. It is characterized by a two stage reaction, requires extracellular calcium and is optimal at 37 degrees C. The rate of release is similar to that of IgE-mediated reactions. Histamine release induced by Staph A is inhibited by metabolic inhibitors, drugs which increase intracellular cyclic AMP levels, inhibitors of lipoxygenase pathways and a phospholipase A2 inhibitor. D2O and cytochalasin B which affect microtubules and microfilaments respectively, enhance histamine release induced by Staph A. These results suggest that Staph A-induced release is modulated by intracellular cyclic AMP, arachidonic acid metabolites, requires energy and is enhanced by the disruption of microfilaments and stabilization of microtubules