Slowing of the contractile properties of skeletal muscle is one of the characteristic features of fatigue. First studied as a slowing of relaxation from an isometric contraction, it has become apparent that this slowing is indicative of functional changes in muscle responsible for a major loss of power with all its functional repercussions. There are three factors contributing to the loss of power in mammalian muscle at physiological temperatures, a decrease in isometric force, which mainly indicates a reduction in the number of active cross bridges, a slowing of the maximum velocity of unloaded shortening and an increased curvature of the force-velocity relationship. This latter change is a major cause of loss of power but is poorly understood. It is probably associated with an increase in the proportion of cross bridges in the low force state but there are no clear candidates for the metabolic changes that are responsible for this shift in cross bridge states. The possibility is discussed that the reduction in activating calcium that occurs with metabolically depleted muscle, alters the distribution of cross bridge states, affecting both shortening velocity and curvature. Muscle function in the body depends on a long chain of command starting from motivation, and even within the muscle fibres there are many steps between electrical activity in the surface and T tubular membranes and the molecular interaction of actin and myosin (Edwards, 1981). It would be wasteful of energy and resources to have certain parts of the chain 'over-engineered' so the different links in the chain are all likely to fail at about the same time when the system is stressed. It is unlikely, therefore, that there is any one site or mechanism of fatigue that applies to every situation. Thus the precise link which fails will vary depending on a range of factors including the type of activity, the type of muscle and the temperature, and when discussing fatigue it is important to specify the preparation and conditions under which the muscle is working. This short review will be concerned with mammalian, mainly human, muscle, undertaking metabolically demanding exercise at physiological temperatures of around 37• C. There have been a number of recent detailed reviews of muscle fatigue mainly David Jones graduated in Medical Biochemistry from the University of Birmingham and completed his PhD in Neurochemistry at the Institute of Psychiatry in London. With a family and house to support he changed fields and went to work at the Royal Postgraduate Medical School on basic muscle physiology and studies of patients with muscle problems. He continued these interests at UCL and in 1993 returned to Birmingham as Professor of Sport and Exercise Sciences; he is currently Emeritus Professor of Muscle Physiology at Manchester Metropolitan University. He has wide interests in muscle and exercise physiology but his abiding concern has been the changes in contractile function that occur with acute fatigue.