Our aim was to study physiological response and acceptability of intermittent muscle contractions. Seven male subjects performed eight isometric handgrip exercises with altered contraction-relaxation periods but identical tension-time products. Local blood flow (BF), heart rate, blood pressure, electromyography, maximal voluntary handgrip contraction (MVC), and venous concentration of potassium and lactate of both forearms were followed during and up to 24 hours after the exercises. Wrist force response to electrical stimulation of a forearm muscle was used to investigate low-frequency fatigue (LFF). Ratings of perceived exertion were recorded during exercise. LFF was associated with a decreased functional capacity, which may be explained by a net potassium loss. Recovery BF was linearly related to mean contraction intensity of the experiments. Physiological criteria for acceptability of isometric exercise are suggested, based on the absence of fatigue during exercise and the return to baseline values within four hours of the recovery period. Based on these physiological criteria, intermittent handgrip contractions at (or higher than) a mean contraction intensity of 17% MVC and continuous handgrip contractions at (or higher than) 10% MVC were considered unacceptable.