We studied the biochemical basis of candidacidal activity by comparing the killing of Candida albicans, a serious pathogen, and Candida parapsilosis, a low-grade pathogen, by human monocytes (Mo) and monocyte-derived macrophages. Mo killed C. parapsilosis significantly better than C. albicans. The two species triggered the respiratory burst and release of myeloperoxidase (MPO) and beta-glucuronidase in Mo to an equivalent extent. In contrast to Mo, macrophages killed both species to an equivalent extent. Mo exhibited a greater candida-stimulated respiratory burst than did monocyte-derived macrophages, and the respiratory burst was required for the killing of both species. 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 less than 0.01 for each). Species differences in resistance to killing by Mo may be related to differences in sensitivity to MPO-derived oxidants, and the ability of C. albicans to resist the effects of these oxidants may be a virulence factor associated with this species.