The course of experimental cutaneous Candida albicans infections produced in mice made leucopenic by the administration of cyclophosphamide was compared to that in untreated animals. In the latter, neutrophils characteristically infiltrated the area of infection and the organisms were virtually always confined to the epidermis. However, even though many fewer foci of infection were associated with neutrophils in the cyclophosphamide-treated animals, a majority of these foci were also unable to penetrate past the epidermis. Although Candida yeast proliferated relatively poorly when cultured in homogenates of skin lacking the epidermis, Candida pseudohyphae could invade into the dermis if inoculated skin was isolated from normal animals and cultured in vitro, or if the epidermis was removed by gentle scraping prior to inoculation with Candida yeast onto the remaining skin of leucopenic animals. Therefore, in the absence of neutrophil contact and killing of Candida pseudohyphae in the epidermis, other cutaneous defense mechanisms appear to be capable of preventing invasion of a majority of the organisms into the dermis. These findings may help to explain why deep Candida infections are rare in patients who have extensive superficial candidiasis.