To investigate the mechanism of aneuploidy that is frequently observed in AIDS, we examined premature sister chromatid separation (PCS), a sign of genomic instability, in peripheral blood cells of HIV-1-infected individuals. PCS was found in all six HIV-1 individuals at a high incidence. When peripheral blood cells from healthy volunteers were infected with HIV-1 in vitro, the incidence of PCS increased. This suggests that HIV-1 infection causes PCS and has the potential to induce aneuploidy.