The influence of short-term high-altitude (HA) residence on intramuscular pH and skeletal muscle enzyme activity of sea-level (SL) residents was investigated. Vastus lateralis muscle samples were obtained by biopsy from rested subjects (n = 5) at SL (50 m) and on the 18th day of HA residence (4,300 m) for determination of glycogen phosphorylase, hexokinase, malate dehydrogenase, and total lactate dehydrogenase activities. A second group of subjects (n = 6) performed cycle exercise of the same absolute intensity (mean +/- SE = 195 +/- 5 W) at SL and on the 15th day of residence at HA. Before and immediately after exercise, vastus lateralis muscle samples were obtained for the determination of intramuscular pH, and venous blood was obtained for determination of lactate concentration. The first group of subjects showed no significant changes in skeletal muscle enzyme activity after 18 days at HA. The second group of subjects were instructed to exercise for exactly 30 min, and all but one could complete the entire bout at SL. However, at HA, none could continue 30 min, and time to exhaustion (mean +/- SE) was 11.9 +/- 1.6 min. Resting intramuscular pH was not significantly different after HA residence as compared to SL. The fall in intramuscular pH was less with exercise on day 15 at HA than during SL exercise. Likewise, the increase in blood lactate concentration with exercise at HA was less than at SL. These data indicate that, after 15-18 days of HA residence, limitations in exercise performance are not due to inordinate intramuscular acidosis or to changes in the activity of glycolytic and oxidative enzymes.