Human immunodeficiency virus type 1 (HIV-1) infects a variety of cell types in vivo. Monocyte/macrophages may be the major reservoir for HIV-1 in the solid tissues of HIV-1-infected individuals. Conflicting data have been reported, though, regarding the presence of HIV-1 provirus in peripheral blood monocytes isolated from HIV-1-seropositive humans. We have evaluated monocytes from the peripheral blood of eleven HIV-1-infected individuals utilizing a new, highly sensitive and specific in situ polymerase chain reaction. We demonstrate HIV-1 provirus in 73% (8/11) of these samples. None of these monocyte samples was demonstrated to contain cells expressing high levels of HIV-1-specific RNA, by standard in situ hybridization. The evaluation of the HIV-1 genome in peripheral blood monocytes of certain infected individuals may assist in the understanding of HIV-1 proviral latency and pathogenesis, in vivo.