Sera of 40 intravenous drug addicts were tested for the presence of cytotoxic antibodies against uninfected and HIV-infected monocytic U937 cells. Twelve out of 31 seropositive samples proved to be cytotoxic for HIV-infected, untreated target cells in the presence of complement. The TNF-alpha treatment of HIV-infected U937 cells increased the detectability of cytotoxic effect of sera (21/31). The complement dependent cytotoxic activity of sera was reduced by pretreatment with recombinant HIV gp120. This reduction proved to be dose-dependent in the majority of cases. Immunofluorescence studies indicated that the cytotoxic sera interacted with antigens mostly localized on the cell membrane of HIV-infected TNF-alpha treated U937 cells. The specificity, the possible role and origin of monocytotoxic antibodies in HIV-infected persons is discussed.