Serial circulating immune complex (IC) determinations were performed in 24 patients with infective endocarditis (IE) using the solid phase Clq, solid phase conglutinin and 3.5% polyethylene glycol precipitation assays. Circulating IC were detected in 67% of IE patients at presentation, but in only 7% of valve lesion controls. Serial determinations produced a 75% prevalence of IC in IE. The presence of circulating IC correlated with "subacute" disease, the presence of tissue deposits of immunoglobulin and/or complement components and with certain extravalvular manifestations (immune complex type glomerulonephritis cutaneous vasculitis and musculoskeletal manifestations). Effective therapy was associated with a fall in circulating IC levels, an effect which was well demonstrated by 3 patients in whom IC rapidly fell to zero following artificial valve replacement. The results support a role for circulating IC in the pathogenesis of this disorder, and suggest that serial IC determinations are useful in following clinical progress, particularly in culture negative endocarditis.