The role of the inflammatory process in the onset of sickle cell crisis has not been fully elucidated, although there is evidence for leukocytosis and enhanced leukocyte to endothelium adhesion. The elevated LEA typical of inflammation may impede recovery from transient ischemic episodes by increasing the resistance to blood flow, which in the case of sickle cell disease may exacerbate the "vicious cycle" of HbS deoxygenation which leads to microvascular stasis. Recent studies on the mechanics of white blood cell margination and adhesion in postcapillary venules of laboratory animals, either in the low-flow state or following tissue exposure to chemoattractants, reveal a marked rise in intravascular resistance with LEA. Such increases may be as great as twofold with as few as 6 WBCs adhering per 100 microns of venule length. In human subjects, leukocytosis attendant to crisis has been correlated with increased time to recover from induced periods of ischemia in skin capillaries. Thus, further definition of the role of the inflammatory process in crisis is needed in light of microvessel obstruction in the low-flow state.