To examine the effect of vascular elasticity on the erythrocyte flow in microvessels, a part of microvascular bed was isolated from rabbit mesentery and treated with 4% formaldehyde. Human erythrocytes suspended in isotonic phosphate buffered saline containing 4 g/dl albumin were perfused through superior mesenteric artery. The erythrocyte flow in the microvessels was observed under an inverted microscope using a video system, and analyzed with an image processor. Erythrocyte velocity was determined by a dual-spot cross-correlation technique.(1) Decreasing hematocrit of erythrocyte suspension, the thickness of cell-free layer increased in both control (elastic) and formaldehyde-treated microvessels. With an increase of microvessel diameter, the cell-free layer increased. (2) Decreasing erythrocyte deformability with diamide by crosslinking spectrin in membrane cytoskeletal network, the cell-free layer decreased. The decrease of cell-free layer was more remarkable at lower hematocrit in control microvessels than in formaldehyde-treated microvessels. (3) When dextran with MW=70,000 was added to suspension medium of erythrocytes, the cell-free layer increased remarkably in 2-4 g/dl in control microvessels. However, the increase of cell-free layer in formaldehyde-treated microvessels was observed in 1-2 g/dl. (4) Overall flow resistance was greater in formaldehyde-treated vascular bed than in control bed. In conclusion, vascular elasticity affects the flow dynamics of erythrocytes in microcirculation and thus the flow resistance.