The purpose of this study was to determine if caffeine (CAF) could enhance exercise performance at high altitude (HA). Eight males (17 to 24 years) performed two submaximal endurance tests to exhaustion (ETX) while cycling at approximately 80% of their altitude-specific maximal aerobic power during each of three phases: 1) sea level (SL); 2) after 1 h (acute) at 4,300 m; and 3) after 2 weeks (chronic) at 4,300 m. Subjects received either CAF (4 mg.kg-1) or a placebo drink 1 h prior to each ETX bout at each phase in a double-blind crossover design. ETX was little affected during CAF treatment at SL (26.33 to 27.51 min, p = 0.21) but was increased by 54% (22.77 to 35.10 min, p = 0.004) during acute HA exposure and tended to improve (24%, 30.52 to 38.63 min, p = 0.084) during chronic HA exposure. The change in ETX during acute ALT could not be accounted for by differences in substrate metabolism, Q, diet, or RPE, but may have been due to either a CAF-induced increase in tidal volume or to a lessening of an ALT-induced impairment in muscular force production during submaximal exercise.