Colony counts and light microscopy were used to assess the capacity of Candida albicans to colonize, infect the alimentary tract, and cause disseminated disease in athymic (nulnu), euthymic (nul+), beige (bglbg), black (bgl+), beige athymic (bglbg nulnu), or beige euthymic (bglbg nul+) germfree mice. The alimentary tracts of all six genotypes of germfree mice were quickly colonized after exposure to yeast-phase C. albicans. Only bglbg nu/nu mice showed obvious morbidity and mortality after mucosal colonization with C. albicans. Histopathology of C. albicans-colonized immunocompetent (nu/+, bgl+) and singly immunodeficient (nu/nu, bglbg, bglbg nul+) mice showed minimal to moderate mucosal infections, whereas doubly immunodeficient (bglbg nu/nu) mice showed extensive yeast and hyphal infection of the palate, tongue, esophagus, and stomach. A progressive systemic infection in C. albicans-colonized mice occurred only in bglbg nulnu mice 12 to 16 weeks after colonization and mucosal infection. Thus, it appears that a combination of defective cell-mediated immunity and phagocytic cell defects (polymorphonuclear leukocytes and/or macrophages) predisposed mice to severe mucosal and systemic candidiasis of endogenous origin. This is the first report of a mouse strain that is not only naturally susceptible to mucosal and systemic candidiasis of endogenous origin but also shows lethality at early (1 to 4 weeks) and late (12 to 16 weeks) times after alimentary tract colonization. tively) females.GF mice were originally derived from NIH BALB/c nude mice, NIH C57BL/6 beige mice, and N:NIH(S) III beige athymic mice by cesarean derivation and have since been 1093 on August 5, 2020 by guest