Defective immunological function of cells of the macrophage lineage contributes to the pathogenesis of HIV-1 infection. Because monocyte/macrophage function is enhanced by cytokines such as interferon-gamma (IFN-gamma), the use of this immunomodulator is of potential clinical interest as adjunctive immunotherapy in immunosuppressed individuals. In this study, we show that adjunctive IFN-gamma treatment in an HIV-infected individual with Mycobacterium avium complex (MAC) infection increased phagocytosis of MAC by blood monocytes when compared to cells from an HIV-infected patient who was receiving standard chemotherapy alone. Enhanced phagocytic efficiency resulting from IFN-gamma therapy was associated with increased surface expression of MHC II (HLA-DR), a phagocytic receptor (CD16), and the activation marker (CD69), although the levels of activation markers were dissimilar at baseline in the two participants. These results imply that IFN-gamma may be useful in restoring antimycobacterial function in immunosuppressed patients.