Population studies have revealed that Candida albicans can be separated into five major clades, groups I, II, III, SA, and E. Groups SA and E are highly prevalent in South Africa and Europe, respectively, while group II is excluded from the southwestern portion of the United State. In each geographical locale, several clades exist side by side, suggesting little interclade recombination. These results suggest clade-specific phenotypes. In the present study we demonstrate that resistance to flucytosine (5FC MIC >/= 32 micro g/ml), an antifungal used for the treatment of systemic C. albicans infections, is restricted to clade I. In addition, while 97% of all strains for which 5FC MICs were >/=0.5 micro g per ml were members of group I, only 3% were members of the other groups. 5FC MICs were >/=0.5 micro g per ml for 72% of all group I isolates, while 5FC MICs were >/=0.5 micro g per ml for only 2% of all non-group I isolates. These results demonstrate for the first time the clade specificity of a clinically relevant trait (5FC resistance) and suggest that while intraclade recombination may be common, interclade recombination is rare.