The existence of an HIV-related nephropathy as a distinct disease entity is controversial. Twelve patients affected by HIV infection (eight drug-abusers, three homosexuals and one black heterosexual) who showed nephrotic syndrome (five patients) or urinary abnormalities (seven patients), four with renal insufficiency, were submitted to renal biopsy. Six patients were in pre-AIDS, six had AIDS. Light microscopy, performed in all cases, showed focal segmental glomerular sclerosis in nine patients, a moderate hypercellularity in six, vacuolisation of visceral epithelium in ten, focal collapsed tuft in seven, and tubular microcystic dilatation with large dense protein casts in lumina in seven. Immunofluorescence, available in 11 patients, showed small deposits in mesangium or mesangial and subendothelial spaces. IgG, IgM, and C3 were more frequently found, while three cases were negative. Electron-microscopy (five patients), besides confirming light-microscopy changes, showed several tubuloreticular inclusions (four patients), nuclear bodies (mainly complex) in nuclei of tubular cells (three patients), and nuclear granulofibrillary transformation of tubular cells. Various histological aspects and clinical data confirm the hypothesis that HIV nephropathy can be considered as a separate entity, different from heroin nephropathy and idiopathic focal glomerulosclerosis.