This prospective study evaluated the in vitro susceptibility of Candida albicans isolates recovered from the oral cavity of AIDS/ARC patients before and during long-term therapy with fluconazole. Thirty adults (15 with ARC and 15 with AIDS) with a first episode of thrush candidiasis were given oral fluconazole (Triflucan 50 mg; one capsule daily) for at least three months. Fungal susceptibility testing was performed before treatment, after one month, and at last follow-up (range 3.5-12 months; mean 5.7 months). MICs were determined using the agar dilution method with casitone (Difco 259-01) as the test medium at pH 7.2-7.4. There were two initial clinical failures (one with high MICs before and under treatment and one with an intermediate MIC initially and a rise in MIC under fluconazole). Four patients developed a clinical relapse with no change in MICs (which were low or intermediate). In six patients, clinical symptoms resolved but carriage of C. albicans persisted (low MICs). In 18 patients, clinical resolution with eradication of C. albicans was achieved. These data suggest that (1) clinical failures may be associated with in vitro resistance; (2) relapses under fluconazole maintenance therapy may develop in patients with advanced HIV disease despite the lack of change in the susceptibility of strains.