Twenty-seven percent of beige-athymic (bg/bg nu/nu) mice died of systemic candidiasis 7-20 weeks after gastrointestinal tract colonization with Candida albicans. Conversely, beige-euthymic (bg/bg nu/+) mice colonized with C. albicans for a similar time period did not die or develop systemic candidiasis. C. albicans-colonized bg/bg nu/+ mice, but not bg/bg nu/nu mice, developed C. albicans-specific T cell-dependent antibody- and cell-mediated immune responses, indicating that T cell-dependent responses might explain the acquired resistance of bg/bg nu/+ mice to systemic candidiasis. Colonization with C. albicans enhanced the resistance of T cell-competent bg/bg nu/+ mice, but not bg/bg nu/nu mice, to systemic candidiasis. T cell-mediated immunity activated after mucosal colonization with C. albicans plays an important role in resistance to systemic candidiasis.