Leukocytes circulate in small numbers compared to red cells and have little effect on bulk blood viscosity except in some leukemias where the ‘leukocrit’ approaches hematocrit. Their main functions are carried out in tissue, and they have evolved specialized adhesive and migratory capabilities to allow recruitment from the blood across vascular endothelium. However, although the cardiovascular system essentially acts as a dispersal system for leukocytes, this does not mean that their mechanical properties are unimportant, or that they cannot influence blood flow. Their slow motion through blood capillaries was recognized early and modern interest in their rheological behavior was spurred by the observations of deformation in human microvessels and glass capillaries made by Bagge, Branemark, Skalak and colleagues [1-3]. It has become evident that these ‘normal’ slow flowing leukocytes can hold up and modify the capillary transit of red cells and influence perfusion and resistance in the microcirculation [4-6]. If perfusion pressures are reduced (e.g., in shock) this slow transit may be reduced to leukostasis [7]. In addition, leukocytes, and especially the most numerous neutrophilic granulocytes, can dramatically change their mechanical properties when ‘activated’ by a variety of agents [8]. Activation at the vessel wall is a necessary part of their physiological migratory response, but if it occurs inappropriately, circulating cells have the potential to cause pathogenic microvascular occlusion [9].

Because of the importance of the mechanical properties of resting and activated leukocytes in the physiology and pathology of the microcirculation, they have been widely studied using rheological techniques. Here we review the theoretical and experimental analyses of leukocyte deformation, and the structural elements that influence the cellular rheology. Physico-chemical factors that influence leukocyte deformation are then described, and the impact of flow resistance on normal and pathological microcirculation is considered.