Twenty-four patients with infective endocarditis (IE) are described, fourteen with Staph. aureus and ten with other organisms. Despite the acute nature of the infection, ten of the fourteen with Staph. aureus IE were hypocomplementaemic; six of these ten had normal levels of C4 associated with low C3 levels, suggesting activation of the alternate complement pathway. Factor B (C3PA) was also low in three of these six cases. In the ten patients with non-Staph. IE, three had hypocomplementaemia with low levels of C4, C3, and Factor B, probably due to C1 (classical pathway) activation with feedback activation of the alternate pathway. In addition, thrombocytopenia was noted in nine of the twenty-four patients and was associated with hypocomplementaemia; the degree of renal insufficiency noted in these patients also correlated with hypocomplementaemia. In Staph. aureus IE thrombocytopenia and hypocomplementaemia, occurring early in the course of the disease, may be due to a non-immune interaction of Staph. cell wall products (Protein A) with immunoglobulin, complement components, and thrombocytes.