The association of Candida albicans with gastrointestinal (GI) mucosal surfaces was studied in vitro and in vivo. The caecal mucosal surfaces from antibiotic-treated and untreated control mice challenged orally with C. albicans revealed that large numbers of C. albicans were associated with the intestinal epithelium of antibiotic-treated mice but not with that of the control mice that possessed an indigenous wall-associated bacterial flora. Moreover, Candida cells only penetrated deep into the mucosa of animals in which the ecology of the intestinal microflora had been disrupted. In mice given antibiotics, C. albicans was associated with the mucosa of all areas of the GI tract; the caecal mucosa had the most associated Candida, whereas the stomach and small intestine had very few associated yeasts. Further examination of caecal mucosa from antibiotic-treated mice showed that C. albicans associated with the mucosa by at least five distinct mechanisms. These included: adhesion to epithelium, adhesion to mucus, co-adhesion to adherent fungi, co-adhesion to adherent bacteria, and entrapment in the mucous gel overlying the epithelium. The cell-surface hydrophobicity of C. albicans also was examined and found not to play a role in Candida adhesion to intestinal mucosa. The predominant association mechanisms appeared to be entrapment in the mucous gel, and adhesion to mucus and the epithelium. The ecological and pathological significance of co-adhesion by C. albicans to attached organisms is unclear but it may be important in the initiation of mucosal lesions.