Twenty patients with infective endocarditis were followed prospectively and all had elevated levels of circulating immune complexes (CICs) detected by staphylococcal binding assay. Mean CIC levels declined for the group as a whole (193 μg/ml ± 24 to 100 ± 17, p < 0.05) and became undetectable in eight patients (47%) who were cured. Patients who died or had complicated courses had higher mean CIC levels at the start and finish (254 μg/ml ± 24 and 145 ± 37) of antibiotic therapy than patients with uncomplicated courses (178 μg/ml ± 19 and 38 ± 24), p < 0.05. CIC levels did not decline significantly in patients with glomerulonephritis or arthritis, in contrast to patients without these features. Despite elevated CIC levels, 10 patients had enhanced mononuclear phagocyte system (MPS) function as assessed by Fc-dependent IgG-coated red blood cell clearance. These data suggest that CICs probably are pathogenic in endocarditis and may contribute to the development of arthritis and glomerulonephritis. Elevated CICs in infective endocarditis do not appear to be directly related to defective MPS function. © 1983.