Eighteen consecutive AIDS patients with a first episode of cryptococcal meningitis were enrolled in the study to evaluate the efficacy and tolerability of amphotericin B with or without flucytosine followed by fluconazole as primary therapy for cryptococcal meningitis in patients with AIDS. The treatment consisted of intravenous amphotericin B 0.6 mg/kg daily with or without flucytosine (150 mg/kg d in four divided doses) for 2 weeks which was then followed by oral fluconazole 400 mg daily for 8 weeks. After completion of primary therapy, all patients received a maintenance dose of oral fluconazole 200 mg daily. The primary therapy was successful in 17 (94%) of the 18 patients. The median length of time to the first negative cerebrospinal fluid culture for Cryptococcus neoformans in the 17 patients with successful treatment was 3 (range 2 to 6) weeks. No patient had to discontinue the treatment due to adverse drug reactions. During a mean observation period of 26.94 weeks, no relapse case was documented among the 17 patients. Our results indicate that this regimen as primary therapy for cryptococcal meningitis in AIDS patients is effective and well tolerated.