The purpose of this study was to determine whether quadriceps or diaphragmatic fatigue or both occur after high-intensity cycle exercise to exhaustion in healthy elderly persons. Ten relatively sedentary male subjects aged 68.3 +/- 1.4 yr (mean +/- SE) (range: 60 to 75 yr) exercised at 65% to 75% of their predetermined maximal work capacity to the limits of tolerance on two separate days. On one occasion, quadriceps twitch force (Q(tw)) was measured during magnetic stimulation of the femoral nerve. On the other occasion, twitch transdiaphragmatic pressure (Pdi(tw)) was measured during bilateral stimulation of the phrenic nerves. Because potentiated twitches may be more sensitive for detecting fatigue, both unpotentiated and potentiated (obtained 5 s after a 5-s maximum voluntary muscle contraction) twitches were measured before and at 10, 30, and 60 min after exercise. During constant-load exercise, subjects exercised at 75 +/- 7 W for 21.9 +/- 1.8 min during the quadriceps studies, and for 17.7 +/- 1.9 min during the diaphragm studies. Peak V O(2) was 1.58 +/- 0.08 L/min during both studies. Pdi(tw) (unpotentiated and potentiated) was not significantly different from baseline at any time after exercise. Unpotentiated Q(tw) was significantly decreased after exercise, to 64.0 +/- 6.3% of the baseline value at 10 min after exercise (p < 0.0003), and remained significantly decreased at 30 min after exercise. Potentiated Q(tw) was also significantly decreased after exercise, to 63.5 +/- 2.7% of the baseline value at 10 min after exercise (p < 0.0001), and remained significantly decreased at 30 and 60 min after exercise. In conclusion, high-intensity cycle exercise to exhaustion results in significant contractile fatigue of the quadriceps muscle but not of the diaphragm in healthy, relatively sedentary, elderly subjects.