Congenitally athymic (nu/nu) mice were inoculated sc with 105 conidia of Fonsecaea pedrosoi and treated orally from the 1st to the 16th week of infection with either a new triazole, SCH39304, or itraconazole at doses of 20 or 60 mg/kg/day. The volumes of the lesions were measured with calipers at 4 week intervals and compared statistically by the Wilcoxon test. At the end of the experiment, mice were killed and samples of the lesions were examined histopathologically and by electron microscopy. Treatment with itraconazole or SCH39304 significantly reduced lesion sizes as compared with controls. There were no differences between the 2 drugs at the dosages used. Histopathologically, lesions of mice treated with either drug had less inflammation with fewer fungi and more diffuse fibrosis than controls. Electron microscopy showed damage to the fungal cell walls in mice treated with itraconazole or SCH39304, characterized by gaps, fragmentation, and delamination. These studies confirm clinical observations that itraconazole is effective in chromoblastomycosis and suggest that SCH39304 should be considered for clinical evaluation.