It has been, and will continue to be, the major objective of this program to elucidate mechanisms underlying hemolytic disorders in humans especially as they may relate to abnormalities in the red cell membrane. In addition more recent interests include studies of the role of activated complement in causing margination of granulocytes in pulmonary capillaries. Specific areas of investigation which will continue to be pursued include: (1) further elucidation of the abnormalities in red cell membrane proteins in hereditary spherocytosis; it is our hope to more fully characterize biochemically the membrane abnormality in this disease, and to use our findings, if possible, to gain understanding into the pathogenesis of other dominantly inherited disorders; (2) we are especially interested in continuing to evaluate the role of accumulated membrane calcium in producing irreversibly sickled cells in sickle cell anemia; our work to date implicates this divalent cation in the production of rigid red cells and ischemic painful crises in this disease; (3) from our work showing that infusion of complement activated by dialysis coils in hemodialysed patients causes neutrophil plugging of pulmonary capillaries, we hope to demonstrate that the "shock-lung syndrome" reflects a similar but endogenous activation of complement with production of secondary pulmonary damage from sequestered and degranulating granulocytes. BIBLIOGRAPHIC REFERENCES: Jacob, H.S., Eaton, J.W., and Yawata, Y.: Shortened red cell survival in uremics: Beneficial and deleterious effects of dialysis. Kidney International. Suppl. 2, 139, 1975.