Mechanisms underlying fatigue development and limitations for performance during intense exercise have been intensively studied during the past couple of decades. Fatigue development may involve several interacting factors and depends on type of exercise undertaken and training level of the individual. Intense exercise (½-6 min) causes major ionic perturbations (Ca(2+) , Cl(-) , H(+) , K(+) , lactate(-) , and Na(+) ) that may reduce sarcolemmal excitability, Ca(2+) release, and force production of skeletal muscle. Maintenance of ion homeostasis is thus essential to sustain force production and power output during intense exercise. Regular speed endurance training (SET), i.e. exercise performed at intensities above that corresponding to maximum oxygen consumption (VO2max ), enhances intense exercise performance. However, most of the studies that have provided mechanistic insight into the beneficial effects of SET have been conducted in untrained and recreationally active individuals, making extrapolation towards athletes' performance difficult. Nevertheless, recent studies indicate that only few weeks of SET enhances intense exercise performance in highly-trained individuals. In these studies, the enhanced performance was not associated with changes in VO2max and muscle oxidative capacity, but rather with adaptations in muscle ion handling, including lowered interstitial concentrations of K(+) during and in recovery from intense exercise, improved lactate(-) /H(+) transport and H(+) regulation, and enhanced Ca(2+) release function. The purpose of this topical review is to provide an overview of the effect of SET and to discuss potential mechanisms underlying enhancements in performance induced by SET in already well-trained individuals with special emphasis on ion handling in skeletal muscle. This article is protected by copyright. All rights reserved.