During the course of a study of oral Candida albicans strains from 60 human immunodeficiency virus-infected patients over a 2.5-year period, 18 of the 295 C. albicans isolates had genomes that failed to hybridize with a C. albicans-specific DNA probe (27A). These strains were germ tube positive and chlamydospore positive and were identified as C. albicans by the ID 32C test (API Systems, Montlieu, France). These strains were analyzed for the presence of two other C. albicans-specific DNA segments by PCR. The first was a C. albicans 1,348-bp species-specific sequence, and the second was a 1,059-bp C. albicans repetitive element. The probe 27A-hybridizing strains yielded PCR products which differed from those of the nonhybridizing strains. Five of these genetically atypical C. albicans strains and 98 of the C. albicans strains were then analyzed for purported virulence factors. The genetically atypical C. albicans strains, in comparison with typical C. albicans strains, produced greater amounts of extracellular proteinase (P = 0.038, Student's t test), adhered to a greater degree to buccal epithelial cells (P = 0.018, Student's t test), and were less susceptible to the antifungal drug 5-flucytosine (P = 0.0003, Mann-Whitney test). Analysis of these strains with other common antifungal drugs showed no statistically significant variation in susceptibility. The results of this study indicated that these genetically atypical C. albicans strains possess increased virulence in comparison with typical C. albicans strains.