In human patients, disseminated candidiasis, a life-threatening disease for immunocompromised patients, is often associated with intestinal lesions. In this study, we demonstrate that immunosuppressed gnotobiotic (IGB) piglets orally inoculated with wild-type Candida albicans developed extensive intestinal lesions and disseminated infection. Severe ulceration of the ileal mucosa was observed overlying regions of colonization and necrosis of the gut-associated lymphoid tissue. Despite the high susceptibility of IGB piglets to many microbial pathogens, an avirulent mutant strain of C. albicans failed to produce intestinal lesions and exhibited poor dissemination, demonstrating that these effects required virulent organisms. It is likely that in IGB piglets, as in human patients, intestinal lesions provide the mechanism for escape of C. albicans from the gastrointestinal tract. Multinucleated giant cells containing fungal organisms were observed within lymph nodes and lymphatic vessels, and as with other pathogens, such cells could provide a mechanism for dissemination of C. albicans.