To examine the question of strain specificity in oropharyngeal candidiasis associated with human immunodeficiency virus (HIV) infection, oral samples were collected from 1,196 HIV-positive black South Africans visiting three clinics and 249 Candida albicans isolates were selected for DNA fingerprinting with the complex DNA fingerprinting probe Ca3. A total of 66 C. albicans isolates from healthy black South Africans and 46 from healthy white South Africans were also DNA fingerprinted as controls. Using DENDRON software, a cluster analysis was performed and the identified groups were compared to a test set of isolates from the United States in which three genetic groups (I, II, and III) were previously identified by a variety of genetic fingerprinting methods. All of the characterized South African collections (three from HIV-positive black persons, two from healthy black persons, and one from healthy white persons) included group I, II, and III isolates. In addition, all South African collections included a fourth group (group SA) completely absent in the U.S. collection. The proportion of group SA isolates in HIV-positive and healthy black South Africans was 53% in both cases. The proportion in healthy white South Africans was 33%. In a comparison of HIV-positive patients with and without oropharyngeal symptoms of infection, the same proportions of group I, II, III, and SA isolates were obtained, indicating no shift to a particular group on infection. However, by virtue of its predominance as a commensal and in infections, group SA must be considered the most successful in South Africa. Why group SA isolates represent 53 and 33% of colonizing strains in black and white South Africans and are absent in the U.S. collection represents an interesting epidemiological question.