Fluconazole (UK-49,858), a new oral bistriazole antifungal agent, was compared with amphotericin B in the treatment of established systemic infection with Candida albicans in normal and diabetic rats. In normal rats, oral fluconazole at 10 mg/kg per day for 7 days reduced Candida colony counts in the kidneys and livers as well as amphotericin B did and was nearly as effective as amphotericin B in a 21-day treatment trial. There was no further reduction in Candida colony counts when normal rats were treated with fluconazole at 40 mg/kg twice a day for 7 days. In streptozotocin-induced diabetic rats, fluconazole at 20 mg/kg per day for either 7 or 21 days compared favorably with amphotericin B in efficacy. Results of our study suggest that oral fluconazole may be useful in the treatment of established disseminated candidiasis in normal as well as diabetic hosts.