The goal of this study was to determine how blocking ATP-sensitive K+ channels with tolbutamide affects the excitability and contractility of intact frog sartorius muscle during fatigue development. Fatigue was elicited with one tetanic contraction every sec for 3 min. During fatigue the resting potential decreased by 10 mV although the action potential overshoot remained constant. The addition of 2 mmol.liter-1 tolbutamide 60 min before fatigue did not modify the effect of fatigue on the resting potential and action potential overshoot. During fatigue development the half-repolarization time of control muscles increased by 0.26 msec in control muscles, although it increased by 0.77 msec in the presence of 2 mmol.liter-1 tolbutamide; the difference was significant. The decrease in force during fatigue development was not affected by 2 mmol.liter-1 tolbutamide (added 60 min before fatigue), whereas the recovery of force after fatigue was slower in tolbutamide- exposed muscles than in control muscles. Addition of 2 mmol.liter-1 tolbutamide after 5 min of recovery reduced the recovery rate of the resting potential and half-repolarization time, but did not affect the recovery of tetanic force during the first 40 min. Our results are consistent with the hypothesis that ATP-sensitive K+ channels are activated during fatigue development and that they contribute to the repolarization phase of action potentials, but they do not support the hypothesis that ATP-sensitive K+ channels contribute to the decrease in force.