The tension time index (TTI) has been used to estimate mechanical load, energy utilization, blood flow and susceptibility to fatigue in contracting muscle. The tension time index (TTI) can be defined, for a rhythmically contracting muscle, as the product of average force development/maximum tetanic force and duty cycle (contraction time/ total contraction and relaxation time). In this study the TTI concept was applied to isolated diaphragm using a method that allowed TTI to be clamped at a pre-determined value. The hypothesis tested was that at constant TTI, muscle energetics and the extent of fatigue would vary with stimulation frequency. Isolated diaphragm strips were stimulated at 25, 50, 75 or 100 Hz for four minutes, 1/sec. Duty cycle was continuously adjusted to maintain TTI at 0.07, which was near the highest TTI tolerated for 4 min, at 20 Hz stimulation. At the end of the fatigue run, muscles were either immediately frozen for [ATP], [Cr] and [CrP] determination (n = 6) or stimulated for evaluation of low and high frequency fatigue (n = 5). Results demonstrate no difference in the extent of fatigue or in the final [ATP] and [CrP] between groups. Large within-run increases in duty cycle were required at low stimulation frequencies, but only small increases were required at the highest frequencies. The results demonstrate that at a constant TTI, similar fatigue properties predominate at all stimulation frequencies with no clear distinction between high and low frequency fatigue. The method of clamping TTI during fatigue may be useful for evaluating energetics and contractile function between treatment groups in isolated muscle when treatment influences baseline contractile characteristics.