We are studying several facets of the functional and metabolic interrelationships of phagocytic cells and potentially pathogenic microorganisms. Special emphasis is placed on human polymorphonuclear neutrophils. Areas of special emphasis include elucidation of specific bactericidal mechanisms utilized in killing of certain organisms. It appears that some organisms are killed most efficiently by cells in an oxygen rich environment while other organisms are killed adequately by oxygen deficient polymorphonuclear neutrophils. This suggests that mechanisms other than hydrogen peroxide and superoxide must be important in the killing of bacteria by leukocytes. Studies are being carried out to look at some of these non-oxidative killing systems with the use of environmental manipulation and cells from patients with phagocytic cell defects where possible. We plan to carefully look at the oxidases responsible for the production of hydrogen peroxide in polymorphonuclear neutrophils to determine the mechanisms for the marked increase of hydrogen peroxide production seen after phagocytosis by normal cells and the lack of increase seen after phagocytosis by cells from patients with chronic granulomatous disease of childhood.