Human immunodeficiency virus-associated nephropathy (HIVAN) is a recognized clinical entity of unknown pathogenesis. A role for viral infection of renal cells in the initiation of this process at present is an intriguing but untested hypothesis. Studies in primate models of acquired immunodeficiency syndrome (AIDS) suggest that injury to the mesangial cell may be central to the sclerosing glomerular lesion characteristic of HIVAN. We therefore tested the infectibility of human mesangial cells (HMC) in vitro by a variety of strains of HIV chosen to include a spectrum of tropisms for different cell types. Productive infection of mesangial cells could not be demonstrated using any of the virus strains. Nonetheless, HIV infection of intrinsic renal cells remains an attractive area of inquiry for understanding the natural history of HIVAN.