Human immunodeficiency virus type 1 (HIV-1) infectivity and cytopathic effect require proper maturation of the viral envelope glycoprotein carbohydrate moieties. We have found that fresh human serum enhances the infectivity of HIV-1 in MT-2 cell infection assays when virus is synthesized in the presence of the mannosidase I inhibitor, 1-deoxymannojirimycin, or the mannosidase II inhibitor, swainsonine, but has no enhancing effect on virus synthesized in the presence of the glucosidase I inhibitors, castanospermine and 1-deoxynojirimycin, or the glucosidase II inhibitor, bromoconduritol. Enhanced infections were characterized by cytopathic effect, antigen synthesis and reverse transcriptase release, all which occurred sooner than in control-infected cultures. This enhancement of infection was also observed in C1q-deficient serum but was not observed in serum that was heat-inactivated or depleted of complement components C3 or factor B, thus suggesting a requirement for the alternate pathway of complement.