Oxidative metabolic changes associated with phagocytosis are essential for the intracellular bacterial killing in human polymorphonuclear leukocytes (PMN). Leukocytes from patients with chronic granulomatous disease (CGD) have normal phagocytic capacity, but fail to show stimulation of oxidative metabolism normally associated with phagocytosis, with impaired intracellular killing of catalase positive bacteria. Little is known about the control mechanisms of oxidative metabolic changes associated with phagocytosis and the underlying defect of CGD leukocytes remains unclear. We have demonstrated the importance of surface sulfhydryl (-SH) groups for the stimulation of hexose monophosphate shunt (HMS) activity and H2O2 production during phagocytosis. We propose to extend our observation and explore further the role of various surface groups (e.g., -SH groups or sialic acids) on the control of phagocytosis associated metabolic changes and intracellular bacterial killing. Our specific aims are: (1) study the effect of P-chloromercurybenzene sulfonic acid, a surface -SH group inhibitor, on: a) superoxide production during phagocytosis, and b) intracellular bacterial killing; (2) study of role of plasma membrane sialic acid, by deleting surface sialic acids with neuraminidase on: a) phagocytosis and its associated oxidative metabolic changes, and b) intracellular bacterial killing; (3) study the effect of endotoxin, taurocholic acid (T.A.) and concanavalin A (conA) on HMS activity of PMN from patients with CGD. We have shown that endotoxin, T.A. and con A stimulate HMS activity of normal PMN at the level of plasma membrane.