Six Rhesus macaques were hyperimmunized with either live infectious human immunodeficiency virus type 1 (HIV-1) or with beta-propiolactone--or formalin--inactivated HIV-1. The virus used was HIV-1 BX08, a primary virus isolate grown in human PBMC. Instead of eliciting virus-neutralizing antibodies, this regimen induced antibodies that enhanced HIV-1 infectivity for PBMC by 10 to 90 fold. Enhancement was also seen in a cell-to-cell fusion assay using a Semliki Forest virus replicon to express BX08 gp160 in CD4+, CCR5+ HeLa cell cultures. These observations raise the concern that whole virus particles-based HIV-1 vaccines might elicit enhancing antibodies that could play a facilitating role in the transmission and/or evolution of the disease.