We used an experimental model of oral candidiasis in the mouse to investigate the impact of the introduction of Candida albicans into a Candida-free system. We report that 2 strains of mice with the same major histocompatibility complex haplotype (H-2d) display different kinetics of primary oral infection after topical application of the same inoculum. The mucosal reactions in both DBA/2 and BALB/c mice involve a similar recruitment of CD4+ and CD8+ T cells and of MAC-1+ cells in mucosal tissue during the infection. A carrier state is maintained following the resolution of the infection in both strains and is associated with the persistence of intraepithelial CD4+ T cells. However, there is a time-specific recruitment of gamma delta T cells that coincides with a dramatic decrease in viable Candida in the mucosal tissue; this occurs on day 3 in BALB/c mice and on day 6 in DBA/2 mice. The denouement of an oral contact with Candida is also different in the 2 mouse strains, cell-mediated immunity being triggered in DBA/2 mice but not in BALB/c mice. The different kinetics of Candida clearance in BALB/c vs DBA/2 mice may therefore signal a differential priming of T cell subsets whose modalities do not appear to be associated with the H-2 complex.