Immune complexes formed in vitro by incubating cell-free human immunodeficiency virus type 1 (HIV-1) with sera from infected or gp160-vaccinated persons, together with normal human serum as a source of complement, readily bound to K562 cells expressing recombinant human complement receptor type 1 (CR1). However, antibodies from seronegative persons had little or no effect. This effect was absent in the presence of heat-inactivated or C3-depleted normal human sera or when wild type K562 cells were used, confirming a requirement for complement and CR1. In additional experiments, complement alone targeted HIV-1 to CR1 on red blood cells, and envelope-specific antibodies increased this effect. These results demonstrate that envelope-specific antibodies promote HIV-1 immune complex formation with complement and that these complexes readily bind CR1 on cell surfaces.