The causative strains in 22 patients with recurrent oral candidiasis were examined using two DNA probes (a Histoplasma capsulatum DNA probe that cross-hybridizes with Candida albicans and a C. albicans strain-specific probe derived from repetitive sequence DNA). C. albicans was the causative organism in all 22 initial episodes of infection and was also obtained from 17 patients with recurrent oral disease. Molecular analysis showed that in 11 cases, the same isolate was identified in each episode. Six patients had a clearly different isolate of C. albicans causing a later episode of candidiasis. Five patients had different Candida species causing recurrent disease: 4, Torulopsis glabrata; 1, Candida parapsilosis. Patients with a new isolate (either new species or a new C. albicans strain) were more immunosuppressed and were significantly more likely (P < .001) than patients with the same recurrent strain to have received suppressive azole antifungal agents. These data indicate that the epidemiology of recurrent candidiasis in individual patients seropositive for the human immunodeficiency virus is complex and that both failure of eradication of Candida from the oral cavity and new infection occur.