Although focal glomerulosclerosis is the most common renal disease, other proliferative glomerulonephritides are encountered in HIV-infected patients. We studied four HIV-infected patients with renal insufficiency, proteinuria, and proliferative glomerulonephritis, consistent with immune-mediated disease, to investigate the role of the virus and immune complexes in the pathogenesis of the nephropathy. Circulating immune complexes (CICs) and HIV-reactive antibodies were measured and characterized in each patient. Renal biopsy tissue was acid eluted, and the eluate analyzed. DNA extracted from biopsies was subjected to the polymerase chain reaction (PCR) to detect HIV genome. CICs were detected in each patient: an IgA-p24 HIV antigen complex and an IgG antibody-gp 120 HIV antigen complex in two patients; two patients had an IgG-p24 HIV antigen complex. Identical complexes were eluted from renal tissue in the first three patients; p24 HIV antigen, and complement from the fourth. The eluted antibodies reacted with the HIV antigens from the isolated CICs. Direct immunofluorescence for viral antigen in the eluted glomerular tissue revealed HIV antigens; PCR confirmed the presence of gag genome in all four biopsies. We conclude both circulating and in-situ HIV antigen-specific immune complexes may be associated with glomerulonephritis in HIV infected patients. Viral incorporation into renal tissue may be important in the pathogenesis of HIV-associated renal disease.