Conidia, produced by the mycelial phase of dimorphic fungi, are thought to represent the infectious form of the organism but must complete a transition to the tissue-invasive, yeast-like phase for infection to ensue. Preventing such transition should effectively eliminate pathogenicity. Using Blastomyces dermatitidis as a target, murine bronchoalveolar macrophages preferentially blocked phase transition after 4 h of incubation with conidia, relatively sparing the ability of conidia to produce hyphae. H2O2, in relatively high concentrations, demonstrated the same activity. The effects of H2O2 seem irreversible, since H2O2-treated conidia that germinated at 48 h at 25 degrees C were still unable to produce yeasts over the next 5 days when incubated at 37 degrees C. Catalase could not reverse the macrophage-induced inhibition of phase transition, suggesting that nonoxidative defense mechanisms may be operative in vivo. Since conidia do not form mycelia at temperatures found in mammalian hosts, these effects may represent a novel host defense mechanism against dimorphic fungal pathogens.