In 85% of adult DBA/2 mice inoculated intragastrically with Candida albicans, significant numbers of yeast cells were recovered from the gastrointestinal tract for up to 4 weeks, with the animals eventually clearing infection in the absence of systemic disease despite the occurrence of localized, self-limiting foci of mucosal involvement in their stomachs. Two major findings in colonized mice were defective production of IgA, interleukin (IL)-4, and IL-5 by Peyer's patches lymphocytes and increased numbers of interferon-gamma-producing T cells in mesenteric lymph nodes and spleens. Relatively low levels of circulating antibodies of T helper type 2 (Th2)-dependent isotypes were also found in colonized mice, which exhibited strong footpad responses and increased resistance to systemic reinfection. Unlike systemic challenge, gastrointestinal colonization of adult immunocompetent DBA/2 mice with C. albicans appears to be an effective stimulus for the systemic development of protective Th1 responses.