Pertussis toxin (PTX) has been used as a reagent to identify involvement of the G protein-mediated signal transduction pathway, In this study, me found that PTX enhanced HIV-1 replication in acute infection systems at a high dose (1-10 mu g/ml) in vitro, PTX treatment enhanced the infectivity of HIV-l-based pseudovirus enveloped with HIV-1 or amphotropic murine leukemia virus (A-MuLV), but not with vesicular stomatitis virus (VSV), This high dose of PTX treatment did not affect HIV-1 gene expression. These data suggested that the effect was virus envelope dependent and that PTX acted on an early stage of viral infection. Treatment with B-oligomer, a nonenzymatic subunit of PTX, mimicked this enhancing effect of PTX, However, desialylation of viral and cellular surface glycoproteins, which are receptors for B-oligomer, did not affect the augmentation induced by PTX, These results indicate that the enhancement of HIV-1 replication is mediated through an unknown biological function of B-oligomer.