Opportunistic fungal infections have emerged as a major cause of sickness and death among certain patients with impaired resistance, including renal transplant recipients and patients with malignant diseases, especially those involving the hematopoietic system. Phagocytic leukocytes appear to constitute a major source of the ability of normal individuals to resist infection by fungal pathogens. In recent years, some of the fungicidal mechanisms of human phagocytes have been elucidated. Best characterized are the oxidative microbicidal mechanisms, that in the neutrophil, include myeloperoxidase and hydrogen peroxide among their active components. We propose to identify and characterize a second class of fungicidal mechanisms in human phagocytes that is non-oxidative in character. Preliminary studies have shown that normal human neutrophils contain a group of fungicidal proteins within their cytoplasmic granules. We hope to determine the nature of these constituents and assess their significance for phagocyte function and their role in the systemic mycoses of man. The long range goal of these studies, in progress for the past five years, is to identify, remedy and ultimately prevent the causes of impaired resistance to infection in man.