1. The purpose of this investigation was to determine if alterations in extracellular calcium (Ca2+) influx by the dihydropyridine derivatives Bay K 8644 and nifedipine affected skeletal muscle fatigue. 2. Tetanic contractions (80 Hz, 100 msec) of frog sartorius muscles were evoked every sec for 3 min. Muscles were fatigued in normal Ringer's solution (NR), in NR containing 1 microM nifedipine of 10 microM Bay K 8644 or in low Ca2+ Ringer's. 3. In each case, the experimental conditions increased the rate and magnitude of fatigue. Rate constants of fatigue obtained during Bay K 8644, nifedipine and low Ca2+ conditions (-.0122 +/- .0016, -.0397 +/- 0022 and 0.0169 +/- .0064 sec-1, respectively) were significantly greater than NR (-.0104 +/- .0006 sec-1, p less than .05). In addition, tetanic forces developed at the end of the stimulation period under the experimental conditions (3.90 +/- 0.81, 1.21 +/- 1.40 and 2.04 +/- 1.10% of initial) were significantly less than NR (7.18 +/- 1.27%, p less than .05). 4. Caffeine contracture forces (10 mM) evoked immediately after stimulation were not significantly different between conditions. 5. These results suggest that alterations in sarcolemmal Ca2+ exchange has some influence on the fatigue process.