Measurements of intravascular pressure, red blood cell (RBC) velocity, and microvessel hematocrit (Hctmicro) were made in arterioles and venules of the cat mesenteric microvasculature during systemic hemodilution (cell-free plasma) and hemoconcentration (packed cells). For a range of systemic hematocrits (Hctsys) from 5 to 67%, changes in volumetric flux of red cells (QRBC) were derived from the product of microvessel bulk flow and Hctmicro. During hemodilution, a heterogeneous response of changes in QRBC was found with larger distributing arterioles (43-54 microns) exhibiting a monotonic fall, whereas increases in QRBC above control were found in smaller arterioles that were indicative of a potential enhancement of oxygen delivery. Although the dilution response of all arterioles and venules averaged for all calibers of vessels demonstrated a decline in QRBC, alterations of Hctmicro suggested a lessening of the disparity between Hctsys and Hctmicro, which was indicative of a more efficient utilization of the remaining circulating RBC volume. In response to hemoconcentration, a decrease in QRBC also occurred, which, in concert with the dilution data, suggested that QRBC was maximized for a range of 28 less than Hctsys less than 46%. From measurements of the arteriovenous pressure drop across mesenteric modules, regional resistance was found to exhibit a relative plateau as Hctsys was increased above its control value. This behavior was attributed to a decrease in vascular hindrance of the principal resistance vessels and an invariance of blood viscosity at the capillary level due to RBC redistribution and the attendant viscous behavior of blood.