Two new antifungal triazoles, BAY n7133 and ICI 153,066, were compared with ketoconazole in treatment of mice challenged intraperitoneally with Cryptococcus neoformans. At high challenge doses, thymus-containing normal mice had prolonged survival after treatment with BAY n7133. Athymic mice, which have severely deficient cell-mediated immunity, were not protected. At low challenge doses, athymic mice also had prolonged survival. Although BAY n7133 was protective, it was less effective than either ketoconazole or ICI 153,066. BAY n7133 was also less effective in mice challenged intracerebrally than in those challenged intraperitoneally. Both ketoconazole and ICI 153,066 prolonged survival and lowered cryptococcal spleen counts to a greater extent than did BAY n7133.