Molecular epidemiology revealed 5 distinct clades among clinical isolates of Candida albicans, using DNA fingerprinting with the complex Ca3 probe. Certain clades were found to be highly enriched in particular geographical areas (e.g., clade E in Europe and clade SA in South Africa, whereas clade II is completely absent in the southwest United States). From fingerprinting data, it is concluded that little interclade recombination takes place, and therefore, it would not be unusual to expect clade-specific phenotypic characteristics. The first clade-related phenotypic difference was found with 5-flucytosine resistance being almost exclusively restricted to clade I. When in vitro antifungal susceptibility testing revealed 8.4% of South African oral yeast isolates to be naturally resistant to amphotericin B, it was decided to investigate a possible clade relationship for this relatively high resistance. Thirty-eight amphotericin B-resistant C. albicans isolates were fingerprinted, and a mixed dendrogram was constructed, including previously fingerprinted isolates of known clade affiliation. With the exception of clade III, resistant isolates occurred in all clades (clade I=3; clade II=3; clade NG=3; and clade SA=29), except clade III. However, the higher number of resistant isolates that clustered in clade SA was statistically significant (P<or=0.02, chi2=11.32).