To investigate the roles of metabolic and nonmetabolic factors in human muscle fatigue, two relatively brief nonexhausting exercise protocols that produced similar levels of moderate fatigue were used: short-duration exercise (SDE; 2-min sustained maximal voluntary contraction) and long-duration exercise (LDE; 15- to 20-min intermittent exercise). After exercise and during recovery, multiple potential mechanisms of fatigue were studied from measurements of voluntary, twitch, and tetanic forces; intracellular metabolites (using 31P-nuclear magnetic resonance spectroscopy); and electromyographic signals. The major findings were as follows. 1) After SDE, fatigue closely correlated with increased [Pi]. Both force and [Pi] recovered within approximately 5 min after exercise. 2) After LDE, force recovered slowly, with significant fatigue beyond 15 min after exercise; however, recovery of [Pi] was not slowed. 3) Electromyographic signals were little affected by either protocol. These findings suggest that multiple mechanisms contribute to moderate fatigue. Fatigue from SDE may arise primarily from metabolic mechanisms, whereas fatigue from LDE involves an additional slowly recovering nonmetabolic mechanism that may arise from impaired activation, beyond the cell membrane, at the level of excitation contraction-coupling.