Staphylococcal protein A, when added to fresh human, guinea-pig, dog or pig serum, caused a marked depletion of complement. This complement consumption, further studied in the human system, was noted only in γglobulin excess. The consumption of individual complement components indicated an activation mechanism similar to the one induced by aggregated human γ-globulin; i.e. a marked depletion of early-acting components. The activation was time- and temperature-dependent. Almost no complement activation was seen using fresh serum from a patient with agammaglobulinaemia. Inhibition of complement activation was noted when protein A was added at equivalence of precipitation or in excess. The dual effect of protein A might be explained by (I) its ability to arrange γ-globulin molecules in a way initiating the complement cascade and (II) inhibition of Fc mediated complement activation by steric hindrance when added in excess. Possible roles of protein A in the pathogenesis of staphylococcal infections are discussed.