We characterized Candida albicans strains responsible for recurrent oropharyngeal candidosis (OPC) in four patients with AIDS who developed clinical and mycological resistance to fluconazole (FCZ). Karyotype and restriction fragment length polymorphism analyses were performed on the clonal populations to differentiate relapse from reinfection, and the results were assessed with those of serotype and FCZ MICs. Despite the polymorphism in chromosomal bands larger than 2.2 Mbp related to an intraclonal variation, karyotype analysis showed a single strain type attributable to each patient. On the other hand, EcoRI and HinfI restriction fragments revealed a polymorphism for one patient between the first sample and the subsequent ones, relevant to the acquisition of a new strain causing the following episodes of OPC. This result coincided with switching of the serotype and with the acquisition of a resistance to FCZ. For the other three patients, the similarity of the DNA electrophoretic patterns and the serotype of the samples suggested that recurrence can be due to the initial strain that generates FCZ resistance. Although useful for epidemiological studies, molecular typing methods seem to be inadequate to detect the acquisition of FCZ resistance.