Cutaneous infection of mice with Candida albicans elicited a predominantly acute inflammatory response, stimulated the production of precipitating antibodies, and conferred protection against subsequent intravenous challenge with the same organism. The acute inflammatory skin reaction seen after cutaneous infection suggested a predominantly humoral response to Candida. Animals infected cutaneously a second time with viable C. albicans developed larger skin lesions than animals infected only once, and the twice-infected animals were more resistant to an intravenous challenge as well. The cutaneous inoculation of mice with heat-killed C. albicans was less effective in stimulating antibody production, in eliciting the inflammatory response, and in inducing a protective response demonstrable by intravenous challenge with viable Candida. This model of experimental candidiasis represents a reproducible means of studying a protective immune response to the organism.