Primary and secondary Trichophyton mentagrophytes dermatophytosis was studied in germfree and conventionally-reared Strain 2 guinea pigs. Although the onset and early development of the primary cutaneous lesions appeared similar in both groups, the T. mentagrophytes monoassociated guinea pigs exhibited more severe skin ulcerations and took twice as long to heal as their conventionally-reared counterparts. Cutaneous reinfection of T. mentagrophytes monoassociated guinea pigs was also protracted; however, these lesions healed in about the same time as a primary infection on conventionally-reared guinea pigs. Germfree guinea pigs, sensitized by cutaneous infection with T. mentagrophytes, manifested 3 correlates of systemic cell-mediated immunity: (1) delayed-type hypersensitivity to intracutaneous injection of trichophytin antigen, (ii) in vitro blastogenesis of spleen and lymph node cells to polyclonal mitogens and Trichophyton antigens, and (iii) allergic contact dermatitis 48 hr following cutaneous reinfection. In an additional experiment, we observed that the time course and severity of a primary T. mentagrophytes infection of germfree guinea pigs was reduced by prior feedings with heat-killed T. mentagrophytes culture. These experiments confirm that the normal microbial skin flora is not required for initiation, development or clearance of T. mentagrophytes dermatophytosis. The disease was protracted and severe in T. mentagrophytes monoassociated guinea pigs, but was abbreviated following either active infection or feeding heat killed mentagrophytes culture. These results support the hypothesis that cutaneous T. mentagrophytes infection is a cell-mediated hypersensitivity disease similar to contact dermatitis.