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Experiments were performed to investigate the influence of isovolemic hemodilution and hemoconcentration on microcirculatory hemodynamics and oxygen transport in the hamster cheek pouch retractor muscle. Measurements of red blood cell velocity, microvessel hematocrit, vessel diameter, segment length (L), hemoglobin oxygen saturation (SO2) and longitudinal SO2 gradient (ΔSO2/L) were made in four arteriolar branching orders before and after isovolemic exchange with plasma (hemodilution) or packed red blood cells (hemoconcentration). In the study of hemodilution, systemic hematocrit was reduced from 52 to 33% in 23 hamsters. This degree of hemodilution resulted in an average decrease in microcirculatory hematocrit from 42 to 28%, and average increases in red blood cell velocity, computed blood flow and systemic arterial oxygen tension (PO2) of 50%, 30% and 10%, respectively. In addition, ΔSO2/L was significantly smaller in second, third and fourth order arterioles compared with control values. It was estimated that about 16% of the oxygen that diffused across the arteriolar network was consumed by the surrounding tissue; the remaining oxygen was presumably transferred by diffusion to nearby venules and capillaries. Following hemodilution, the proportion of the diffusional loss that was consumed by the periarteriolar tissue increased to about 27%. Convective oxygen flow remained at its control level in the first order arterioles, and progressively increased above control with increasing branching order. The increased oxygen delivery to the capillary network following limited hemodilution can be attributed to a compensatory increase in blood flow, an increase in systemic arterial blood oxygenation, and a decrease in precapillary oxygen loss. In the study of hemoconcentration, systemic hematocrit was increased from 50% to 65% in 17 hamsters. Microcirculatory hematocrit increased from 40% to 50%, while the average red blood cell velocity and computed blood flow decreased approximately 40% and 30%, respectively. ΔSO2/L significantly increased in the four arteriolar branching orders compared with control values. It was estimated that about 10% of the oxygen that diffused across the arteriolar network was consumed by the surrounding tissue; the remaining 90% was presumably transferred by diffusion to nearby venules and capillaries. Convective oxygen flow again remained at its control level in the first order arterioles and progressively decreased below control in the more distal branching orders. Our analysis of arteriolar oxygen diffusion indicated that tissue oxygenation was unchanged following hemoconcentration, a result that can be attributed to a combined effect of decreased red blood cell velocity, increased precapillary oxygen loss, relatively unchanged diffusional shunting and arteriolar vasodilation. It appears that oxygen diffusion from arteriolar networks may play an important role in the regulation of tissue oxygenation during alterations of systemic hematocrit.