The fungicidal activity of murine polymorphonuclear neutrophils from the peripheral blood or elicited intraperitoneally with thioglycollate or with antigen in Paracoccidioides braziliensis-sensitized or nonsensitized mice was studied. Although peripheral blood, thioglycollate-elicited, and antigen-elicited neutrophils from normal mice or thiogly-collate-elicited neutrophils from P. braziliensis-sensitized mice killed Candida albicans (57% to 84%), they failed to significantly reduce inoculum colony forming units of P. braziliensis (0% to 13%). In contrast, antigen-elicited neutrophils from sensitized mice reduced colony forming units of P. braziliensis by 40%, and exhibited significantly enhanced candidacidal activity compared to thioglycollate-elicited neutrophils from normal or sensitized mice but not peripheral blood neutrophils from normal mice. Fresh serum, but not specific antibody, was required for optimal killing of P. braziliensis, presumably representing an essential role for complement. Killing of P. braziliensis by antigen-elicited neutrophils from sensitized mice correlated with their ability to produce an enhanced oxidative burst, as measured by luminol-assisted chemiluminescence, when interacting with killed P. braziliensis cells. These results indicate that in P. braziliensis-sensitized hosts an inflammatory reaction to P. braziliensis results in activation of neutrophils for significant killing of the pathogen.