Invasive candidosis poses a serious threat to immunocompromised patients. We studied the functional and biochemical basis of phagocytosis and killing of candida by human monocytes (Mo) and monocyte-derived macrophages (MDM). We found that opsonized candida species were ingested equally by Mo and MDM, but uptake of unopsonized candida was mediated only by MDM, primarily through the macrophage mannose receptor. Mo killed C.parapsilosis, rarely pathogenic, significantly better than C.albicans, a serious pathogen. In contrast to Mo, macrophages killed both species to an equivalent extent. The two species triggered the respiratory burst and release of myeloperoxidase (MPO) to an equivalent extent. C.parapsilosis was killed much more easily than C.albicans by exposure to low concentrations of hypochlorite or monochloramine, MPO-dependent oxidants released by Mo but not macrophages, which lack MPO. With six different candida strains there was a significant correlation between killing by Mo and susceptibility to hypochlorite (r=0.926) or monochloramine (r=0.981)(p<0.01 for each). Therefore, we hypothesized, that the capacity of macrophages to kill candida might be retained in the presence of MPO and studied the ability of rhMPO to augment the fungicidal activity of resident and rhGM-CSF-activated macrophages for C.albicans. Addition of rhMPO (concentrations: 0.8, 1.6, 3.2, and 6.4 U/ml) to suspensions of resident macrophages and serum-opsonized C.albicans resulted in significant increases in the killing of candida at concentrations of 3.2 U/ml and 6.4 U/ml(p<0.05 for each). Addition of rhMPO (concentrations: 0.8 to 6.4) to activated macrophages further increased the candidacidal capacity of rhGM-CSF-activated cells (p<0.05 at each concentrations used). These data indicate that exogenous rhMPO augments candidacidal capacity of both resident and rhGM-CSF-activated macrophages with a more profound effect on activated cells. These data suggest that rhMPO might be effective in the treatment of invasive candidiasis.