Recent advances in cancer chemotherapy, in organ transplantation and in the treatment of immune deficiency diseases have increased the longevity of patients but have also created new medical problems of considerable magnitude. Candida albicans, a yeast which is commonly found as a component of the indigenous microflora of humans, is a frequent cause of superficial lesions or generalized systemic infection in patients who are undergoing treatment for these disorders. Mucocutaneous and systemic candidiasis are therefore potential health hazards in such compromised individuals. It has been estimated, for example, that more than 50% of cancer patients undergoing combined surgical procedures and chemotherapy develop widespread Candida infections, and upon examination at autopsy about half of those who succumb have pathological lesions suggesting that candidiasis was a primary cause of death (Remington and Andersson, 1976). Investigations of candidiasis have been hampered by the lack of a suitable animal model. We have been successful in showing that infant mice can be chronically or lethally infected following oral challenge with C. albicans and propose to examine the dynamic host-pathogen interreactions in this experimental system. Animals infected with highly virulent strains (i.e., given lethal infections) will be examined so as to establish the process of colonization using both histological and ultrastructural techniques. The pathology of the disease also will be studied and the possible contributions of cell associated or secreted toxins evaluated. Chronic infection in infant mice will be induced by challenge with strains of diminished virulence and then they will be compromised by a variety of treatments including X-irradiation, broad spectrum antibiotic therapy, and treatment with drugs for cancer chemotherapy and for immunosuppression. We also have been able to achieve infection in treated adult mice following oral challenge. Many of the same studies proposed for infant mice will be carried out using adult animals. This will provide the necessary background for investigations of active immunity to candidiasis and the evaluation of various candidal components as potential immunoprophylactic agents.