The efficacy of oral fluconazole versus nystatin was evaluated as a treatment modality for oral candidosis. Of the included patients (n = 60), two-thirds presented with an erythematous candidosis, and the others showed clinical signs compatible with a pseudomembranous candidosis. Predisposing factors were xerostomia (n = 18), HIV (n = 5), immunosuppression in conjunction with organ transplantation (n = 10), and wearing of dentures (n = 14). For the remaining patients no specific predisposing factors were found. One patient who was treated with nystatin was excluded owing to nausea that was related to the antifungal treatment. After 7 days of treatment with fluconazole (50 mg/day), the affected oral mucosa, assessed by the investigator, was cured or showed considerable improvement in 87% of the patients (n = 30). The corresponding figure for the nystatin group (n = 30), rinsing with 1 mL 4 times a day for 21 days, was 80%. Following treatment with fluconazole, 20 of 22 patients with symptoms at the start (91%) reported improvement. The comparable figures for the nystatin group were 10 of 12 patients (83%). Half of the patients in the nystatin group reported inconvenience from taking the medication (mean value = 25.9) compared with 23% of the patients in the fluconazole group (mean value = 6.6). Eight patients in the fluconazole group and 12 patients in the nystatin group exhibited a relapse within 6 months. These differences were not found to be statistically significant. The patients in the fluconazole group reported less inconvenience from taking the medication, a finding that may have clinical implications for compliance.