The efficacy of fluconazole and amphotericin in the management of denture stomatitis was investigated in a comparative trial. Patients were assessed clinically, hematologically, and mycologically at the time of entry into the study and at 1, 4, and 12 weeks thereafter. A total of 29 patients were selected at random to receive 50 mg of fluconazole daily for 14 days; 30 patients were selected to receive amphotericin lozenges and cream for 28 days. Clinical response rates were similar in both treatment groups throughout the study. The best mycologic response was noted after 1 week whereas the best clinical response was observed after 4 weeks. Clinical evidence of relapse and recurrence at 12 weeks was a common finding irrespective of treatment. Side effects were uncommon in both groups.