Radioimmunotherapy (RIT) prolongs the survival of mice infected with Cryptococcus neoformans. To compare the efficacy of RIT with that of amphotericin B, we infected AJ/Cr mice intravenously with either nonmelanized or melanized C. neoformans cells. Infected mice were either left untreated or treated 24 h after infection with (213)Bi-18B7 antibody, amphotericin B, or both. Melanization before infection did not increase resistance of C. neoformans to RIT in vivo. (213)Bi-18B7 treatment almost completely eliminated colony-forming units from the lung and brain, whereas amphotericin B did not decrease the number of colony-forming units. We conclude that RIT is more effective than amphotericin B against systemic infection with C. neoformans.