In primary cultures of Kupffer cells obtained from surgical biopsies of human liver by collagenase perfusion followed by centrifugal elutriation and infected with HIV, the virus multiplied abundantly, as attested by the appearance of a reverse transcriptase activity in the medium. Examined by electron microscopy, the cells were found to contain viral particles with typical features of Lentivirinae. Furthermore, the virus could be revealed by immunofluorescence using an HIV+ patient serum. HIV antibodies also neutralized the infectivity of the Kupffer cell-produced virus. Our results demonstrate that the cells constituting the largest fraction of fixed macrophages in the body may be infected by HIV, thereby suggesting that the Kupffer cells may play a role in the physiopathology of the disease, namely as a reservoir for the virus.