The effects of unequal distribution of blood flow on O2 uptake are studied on a model composed of 3 tissues compartments with blood flow/O2 requirement ratios in the relation 9:3:1 (unequal blood flow model), a model with 33% shunt blood flow (shunt model), and a single compartment model without shunt (reference model). Diffusion limitation is assumed to be absent. Total blood flow (Q), arterial O2 content (CaO2) and O2 requirement of tissue are varied singly, and the resulting (mixed) venous O2 content (CvO2) and O2 uptake are calculated. In the reference model, CvO2 become zero, and O2 uptake starts falling below the O2 requirement, as soon as the O2 delivery (Q.CaO2) becomes smaller than the O2 requirement. In contrast, in the unequal blood flow model, decrease in the ratio O2 uptake/O2 requirement and in CvO2 sets in earlier, and proceeds more gradually, with decreasing Q or CaO2 or increasing O2 requirement; this is, because O2 delivery limitation sets in sequentially in the compartments, starting with the least perfused compartment. The shunt model behaves similarly to the reference model if Q or O2 requirement is varied, and to the unequal blood flow model if CaO2 is varied. Some features such as the parallel fall of O2 uptake and of CVO2 with decreasing CaO2, common to the unequal blood flow and shunt models, are similar to expected effects of diffusion limitation. Therefore, when the influence of diffusion limitation on tissue O2 supply is to be investigated quantitatively, the effects of a possible unequal distribution of blood flow must be taken into account.