Hartley strain, male guinea pigs were cutaneously infected at the nape of the neck with T. mentagrophytes var. granulosum. Guinea pigs were also immunized with keratinases (I and II) in Freund’s complete adjuvant. Guinea pigs sensitized by cutaneous infection developed dermal reactivities of the delayed type, the most intense reaction being to the heat-inactivated keratinase II. The cutaneous reactions to both keratinases were greater than the reactions to commercial trichophytin. No circulating antibodies to the enzymes or commercial trichophytin were detected by immunodiffusion or complement fixation analyses. Guinea pigs immunized with active keratinases had both dermal reactivities and circulating antibodies to the keratinases. Dermal reactivities were detectable seven days after immunization. Circulating antibodies were later detectable by immunodiffusion and complement fixation. Serum γ-globulins from immunized guinea pigs also inhibited the proteolytic activities of the keratinases. Neither delayed cutaneous reactivities nor circulating antibodies to the keratinases were detected in control guinea pigs.