A continual hydrolysis and release of FFA from the triglycerides stores of adipose tissue occurs during prolonged moderately severe exercise. The uptake and oxidation of plasma FFA by the working skeletal muscles represents a major source of energy during such exercise. During light and moderately intense prolonged exercise, lipolysis and the release of FFA from the adipose tissue exceeds uptake by peripheral tissue and the net result is an increase in plasma FFA levels. FFA uptake appears to be related to plasma concentrations and uses no membrane transport system. As work intensity increases the release of FFA from adipose tissue declines and the relative contribution of the plasma FFA to the work metabolism declines until at high work rates there is an almost complete reliance on the intramuscular glycogen reserves. At work loads above about 65% of the individual's aerobic capacity the limiting factor for prolonged exercise appears to be the glycogen stores of the working muscle. When these stores are depleted the work either must stop or its intensity be reduced. Trained individuals have a greater capacity to oxidize fats at high work loads than do untrained subjects. This, however, is not matched by an increased capacity for lipolysis. Why intramuscular glycogen stores are required for prolonged relatively severe exercise when the amount of FFA and glucose that perfuses the skeletal muscles under such conditions is theoretically capable of supporting the exercise metabolism is unknown.