The ability of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and gamma interferon (IFN-gamma) to modify human immunodeficiency virus (HIV; also called HTLV-III/LAV) infection in the monocytic cell line U-937 was examined. When added to persistently infected cell cultures, GM-CSF at 30-300 units per ml produced maximal reductions in reverse transcriptase activity of 37-55% 10-14 days after its addition, whereas IFN-gamma produced reductions of 64-68% 10-17 days after addition. When used prior to acute HIV infection and maintained in the cell culture system, these cytokines reduced reverse transcriptase activity 90-100% and nearly eliminated viral antigen expression but did not prevent return of productive infection after their removal. These results indicate that, in a monocyte model of HIV infection, GM-CSF and IFN-gamma substantially restrict HIV expression and that these cytokines deserve further evaluation as therapeutic alternatives in HIV-related disorders.