Background. Skeletal muscle ventricles (SMVs) working as aortic counterpulsators have provided long-term left ventricular assistance under experimental conditions. However, gradual deterioration of SMV pump function and rupture have beers observed, and this may be related to compromised intramural blood flow during synchronized counterpulsation under systemic working conditions. Methods. Transformed, double-layered SMVs in 6 sheep were stimulated for 3-minute periods (5 V, 30 Hz, burst duration and delay from QRS both 40% of the cardiac cycle) to work as diastolic counterpulsators in the systemic circulation at a 1:2 (SMV:heart) and 1:1 ratio, and on a mock circulation with low-pressure loading conditions at a 1:2 ratio. Thoracodorsal artery blood flow was monitored by ultrasonic flow probe, and intramural blood flow distribution was investigated by fluorescent microspheres. Thoracodorsal venous lactate concentrations were measured before and after each period of stimulation. Results. Thoracodorsal artery blood flow increased significantly (p < 0.001) after stimulation. The magnitude of augmentation (89%; 95% confidence interval, 36% to 163%) was similar for all working conditions studied. Reactive hyperemia was observed after most 1:1 regimens but was pare after 1:2 regimens. A significant (p < 0.05) 15% increase in serum lactate levels was present after 1:1 regimens only. All regimens of stimulation resulted in a significant increase (p < 0.01) in blood flow to sections in the outer wall of the SMV, but a significant increase ((p < 0.05) in blood flow to sections in the inner wall was observed only under low loading conditions. Conclusions. Skeletal muscle ventricles subjected to 1:1 systemic counterpulsation regimens work under partly anaerobic conditions. High loading conditions may compromise SMV inner wall blood flow.