Involvement of neutrophils and delayed hypersensitivity in the clearance of Candida albicans infections was investigated with the use of a model of the disease in inbred mice. Experimental infections were produced by rubbing C albicans onto the shaved skin of the flank without the use of occlusive dressings. After a single infection, delayed hypersensitivity to Candida developed in C57BL/6 mice, and the infection cleared more rapidly than in C3H/He mice, in which delayed hypersensitivity did not develop. In both strains, the organisms were associated with neutrophilic microabscesses in the upper epidermis within 1 day of inoculation; by 3 days, the organisms and microabscesses had become relocated to a site just above the skin surface. At this time, the epidermis was intact under the microabscesses and significantly thickened, which indicated that epidermal proliferation had occurred. Delayed hypersensitivity reactions accelerated clearance of the infection, apparently by increasing the rate of removal of the microabscesses and associated organisms from the skin surface. However, delayed hypersensitivity was not an absolute requirement for clearance, because in animals of the C3H/He strain, in which delayed hypersensitivity did not develop during the first infection, the infection was eventually cleared. It is postulated that in these infections an important defense mechanism may be the enhancement, perhaps by the neutrophilic infiltrate, of epidermal proliferation early in the infection such that the infecting organisms are moved to a location above the skin surface from which they can be more easily removed by other processes, including delayed hypersensitivity reactions.