We have developed a novel system to study monocytic function after human immunodeficiency virus type 1 (HIV-1) infection by infecting a series of human macrophage hybridoma cell lines with HIV-1. Since ethanol has detrimental effects on immune function, we investigated the effect of ethanol and its metabolites acetaldehyde and acetate on monocytic function by utilizing one human macrophage hybridoma cell line, clone 43, as well as primary monocytes. Pretreatment of clone 43 and primary monocytes with ethanol and its metabolites resulted in diminished accessory cell function for mitogen-, anti-CD3-, and antigen-induced T-cell proliferation. The decreased accessory cell function was associated with reduced interleukin 1 (IL-1), IL-1, and tumor necrosis factor alpha production with loss of intracellular cytokine and mRNA production and the induction of transforming growth factor . In ethanol-, acetaldehyde-, and acetate-treated HIV-1-infected clone 43 cells (43_HIV), there was a more rapid loss (3 days after infection) of accessory cell function at a lower infecting dose of HIV-1 than that in untreated 43_HIV cells. We also observed a more rapid loss of surface class II antigen expression in the ethanol-, acetaldehyde-, and acetate-treated 43_HIV cells, but no change in surface expression of CD80 or CD86. Ethanol-induced impairment of monocytic function may compound the immunologic defects of AIDS, making the infected individual more susceptible to the complications of the disease.