Several renal pathologic entities have been reported to be associated with human immunodeficiency virus (HIV) infection. The most common is focal glomerulosclerosis, but several different types of glomerulonephritis have been observed in patients with HIV infection and the acquired immunodeficiency syndrome. The mechanisms involved in the pathogenesis of the kidney disease remain obscure. We studied an HIV-infected patient treated with interferon-alpha who had developed proteinuria and membranoproliferative glomerulonephritis to determine whether the renal disease was associated with HIV infection or with chemotherapy. Circulating HIV antibodies were assessed by enzyme-linked immunosorbent assay; circulating immune complexes (CICs) were measured by C'1q assay and isolated by polyethylene glycol precipitation, then subjected to gel electrophoresis and immunochemical analysis. Renal biopsy tissue underwent acid elution, and the eluates were analyzed similarly. In addition the eluted antibody and the antibody from the CIC were assessed by immunodiffusion with eluate and immune complex antigens. A single CIC was detected, which was composed of an immunoglobulin G antibody complexed to a 26-kd protein antigen that was shown to be interferon-alpha. Eluate from the renal biopsy tissue demonstrated identical material, which cross-reacted with the components of the isolated CIC. Immune complex renal diseases, such as membranoproliferative glomerulonephritis, may be related to biologic response modifying agents in patients with HIV infection. The relative roles of their biologic response modification and the disordered immunoregulation seen in such patients in the pathogenesis of the renal disease is unclear. Renal biopsy is necessary to assess the etiology of the renal disease in HIV-infected patients.