We have established a program to make human monoclonal antibodies to the human immunodeficiency virus (HIV). Lymphocytes of lymph nodes from patients with the acquired immunodeficiency syndrome (AIDS) related complex (ARC) spontaneously produced antibodies to HIV in vitro and their antibody production was suppressed by culturing them in the presence of HIV antigens. Therefore, in vitro stimulation with HIV antigens was not done but rather, donor lymph node or spleen lymphocytes were directly fused with mouse myeloma cells. One of the hybridomas thus generated has been stably producing human monoclonal antibody (MAb) of the IgG1 isotype with a kappa chain. This antibody, MAb86, bound to the surface membrane of HIV-infected cells but not to that of uninfected cells at all. MAb86 reacted in Western blot with both viral glycoproteins of 120,000 daltons (gp120) and 41,000 daltons (gp41). While not neutralizing alone, a combination of MAb86 with another human IgG1 MAb against gp120 showed viral neutralization. Based on these data it seems likely that this approach will result in human MAbs capable of viral neutralization and antibody-dependent cytotoxicity. These may have value for the prevention and/or treatment of AIDS.