Introduction: Laryngeal histoplasmosis was first described in 1952. Since then, fewer than 100 cases had been reported. This dimorphic fungus is endemic in the Mississippi and Ohio River Valleys. The yeast phase is responsible for human infection.Methods: We report a 44-year-old woman who developed laryngitis. The markedly abnormal larynx, which could have been mistaken for papillomatosis, was biopsied, at which time the diagnosis of histoplasmosis was confirmed. Treatment with oral ketoconazole was instituted.Results: Objective voice assessment showed abnormalities of maximum phonation time, speaking fundamental frequency, perturbation, percent voicing, mean flow rate, and spectral pattern. Subsequent to antifungal therapy, objective measures were improved.Conclusion: This represents the first case of laryngeal histoplasmosis in which response to therapy is documented by objective vocal assessment.