The intranasal route was used to study Candida albicans infections in mice. Mice from two different inbred strains were challenged intranasally with C. albicans and the level of local and systemic colonization was monitored. DBA/2 mice were highly susceptible to challenge and viable C. albicans disseminated from the lungs to deeper tissues, including kidneys, liver and spleen within 48 h. In contrast, in BALB/c mice challenged in the same manner, C. albicans were retained within the lungs and cleared. Local and systemic anti-C. albicans immune responses were investigated. BALB/c mice exhibited higher titres of serum and mucosal anti-C. albicans IgA than DBA/2 mice. Splenocytes from BALB/c mice, but not from DBA/2 mice, produced detectable levels of interleukin-4 and -5 following stimulation with C. albicans antigens. Both DBA/2- and BALB/c-derived splenocytes produced interferon-gamma and interleukin-10 in response to similar stimulation. In conclusion, the intranasal route provided a simple, non-invasive murine model for investigating C. albicans infection through mucosal surfaces.