Human as well as experimental studies were performed to evaluate the effects of reduced blood flow on skeletal muscle metabolism. Claudicating patients had a lower oxygen tension and energy state in the gastrocnemius muscle in relation to the work performed during leg exercise, as compared to normal subjects. At a certain oxygen tension, however, the patients were able to maintain a lower [lactate]/[pyruvate] ratio in the muscle tissue, which was ascribed to their higher capacity for oxidative metabolism. Perfusing the contracting rat hindlimb at reduced blood flow showed more pronounced changes in the energy and redox-state in the gastrocnemius muscle than in the soleus muscle. This shows that a muscle composed of fast glycolytic fibers is more susceptible to a reduced flow during exercise than one composed of slow oxidative fibers and suggests that the claudicating pain is located in the former. Repeated exposure of rat muscles to reduced blood flow during exercise caused chronic changes in oxidative enzyme activities, in line with the adaptive changes found in claudicating patients.