Marked functional changes occur in human skeletal muscle during prolonged repetitive exercise. The maximum voluntary contraction force (MVC) falls gradually and may reach 50% of control within 30-60 min. The twitch tension declines faster and to a larger extent. During repetitive submaximal isometric contractions the rate of relaxation increase progressively, in parallel with an increased energy cost of contraction. These functional changes are all slowly reversed in the post-exercise period, as indicated by only minor changes over the first 30 min of recovery. Minor changes in substrates and metabolites, together with the slow rate of recovery, indicate that the alterations in contractile properties and energetics are independent of these metabolic factors. Alternative explanations may be related to electrolyte shifts over the sarcolemma or between cellular compartments. The total loss of K+ is small, and could not be detected by analysis of muscle biopsies. Only a slight initial rise in muscle content of calcium was found. The available data indicate that the increased energy cost of contraction is not connected to mitochondrial dysfunction, which might be caused by calcium accumulation. Rather, it seems that the ratio of ATP utilization to force is increased and this could possibly be connected to this faster relaxation rate. Considering the low excitation rates during submaximal voluntary contractions, each motor unit generates an oscillating force closely associated with Ca2+ fluctuations between SR and cytosol. Increased relaxation rats might be caused by faster reuptake of Ca2+ into the SR, and this could contribute to the faster ATP turnover.