Human immunodeficiency virus type 1 (HIV-1) infection causes immune dysfunction. Mononuclear phagocytes (MNP) are immune effector cells against some intracellular pathogens and reservoirs for HIV-1. This study determined effects of HIV-1 on MNP-mediated antifungal function. MNP from seronegative volunteers were inoculated with HIVBal or HIVIIIB. MNP were infected with an avirulent clone of Cryptococcus neoformans; 48 h later, MNP were lysed and yeasts were counted. Viral replication was determined by reverse transcriptase and by visualization of cytopathic effects. Monocytes and peritoneal macrophages exhibited reduced anticryptococcal activity 14 days after infection with HIVBal but retained normal activity when infected with HIVIIIB. Loss of anticryptococcal activity correlated with viral replication. Alveolar macrophages retained normal anticryptococcal activity whether infected with HIVBal or HIVIIIB. In vitro MNP-mediated antifungal activity may be altered by HIV-1 infection; this altered activity appears to depend on viral tropism, viral replication, and MNP tissue origin.