Three separate, but related, projects involving alterations in blood-cell membranes will be pursued during the tenure of this grant: 1) We will attempt to elucidate the role of 2 interacting red cell membrane proteins, actin and spectrin, in regulating the shape and survival of red cells; we particularly hope to demonstrate that excessive membrane Ca 2 ion generates an abnormally rigid latticework of spectrin-actin complexes which, in turn, produces irreversibly sickled cells in Sickle Cell Anemia and perhaps spherocytes in Hereditary Spherocytosis. 2) We will investigate the effect of activated complement (C') components on neutrophil function and distribution; we believe the "shock-lung" syndrome is caused by C'-induced neutrophil plugging of pulmonary capillaries with subsequent lysosomal enzyme release resulting in endothelial damage; pharmacologic methods of blocking excessive neutrophil adhesiveness to pulmonary endothelium are to be evaluated in an attempt to prevent this syndrome. 3) Finally, we shall study the mechanism of hemolysis in hyperbilirubinemic infants undergoing phototherapy. The possibility that photodegradation of bilirubin produces red cell-damaging oxidants which accumulate particularly in infants with renal-insufficiency will be examined.