A 2.5-month-old previously healthy female infant presented with serositis , nephrotic syndrome, progressive renal failure, anemia, and thrombocytopenia. Renal biopsy revealed a proliferative glomerulonephritis with glomerular and extraglomerular deposits of IgG, IgM, C3, and Clq by direct immunofluorescence (IF) techniques. Skin biopsy was positive for IgG and C3 deposits in the dermal-epidermal junction by IF. Despite strong clinical and pathological criteria for systemic lupus erythematosus (SLE), tests for antinuclear and anti-DNA antibodies were negative. Circulating immune complexes (CICs) were detected in three separate assay systems. Immunochemical analysis of isolated CICs showed that anti-DNA antibody was present. Analysis of kidney biopsy material by antigen-specific solubilization techniques showed antibodies reactive with ds-DNA in the kidney. These studies confirm that SLE may be a cause of the congenital nephrotic syndrome and that negative SLE serologies may be secondary to binding of available antibody by excess antigen. Analysis of CICs may be helpful in confirming the diagnosis of SLE in seronegative patients.