The pathophysiology of vascular occlusion events in sickle cell anemia is not completely understood. The objective of this proposal is to determine whether the shearing action experienced by red cells in the microvasculature interferes with sickle hemoglobin gelation and thereby ameliorates the deformability of sickle erythrocytes in vivo. The specific aims are: 1) To study the evolving morphology of sickle erythrocytes (SRBC) as they are deoxygenated under shear in the rheoscope and thereby to delineate the role of shear in the kinetics of intracellular HbS gelation. 2) To quantitate the deformability of individual SRBC as a function of their PO2-time history. 3) To investigate how the shear effect, if demonstrated, is affected by manipulations of SRBC water and ion content. Direct microscopic observations and video recording of red cells tank-treading at various shear stresses are accomplished by means of a counter - rotating cone-plate rheoscope. From enlarged photographs and video tapes, cell extensibility, tank-treading frequency and recovery time after cessation of flow are determined. To effect a change in hemoglobin saturation while the cells are exposed to shear stress in the rheoscope two techniques will be used. In one, the PO2 of the gas mixture flowing through the rheoscope is decreased. The other technique maintains the PO2 constant but increases the temperature in the rheoscope from 22 degree C to 38 degree C. The deformability of tank-treading cells are quantitated as a function of time after initiation of a change in saturation.