The purpose of this investigation was to determine the effect of caffeine ingestion on work output at various levels of perceived exertion during 30 min of isokinetie variable-resistance cycling exercise. Ten subjects completed six trials 1 hr after consuming either 6 mg · kg−1 caffeine (3 trials) or a placebo (3 trials). During each trial the subjects cycled at what they perceived to be a rating of 9 on the Borg rating of perceived exertion scale for the first 10 min, a rating of 12 for the next 10 min, and a rating of 15 for the final 10 min. Total work performed during the caffeine trials averaged 277.8 ± 26.1 kJ, whereas the mean total work during the placebo trials was 246.7 ± 21.5 kJ (p < .05). Blood glycerol and free fatty acid levels increased over time to a significantly greater degree in the caffeine trials than in the placebo trials (p < .05). However, there were no significant differences between conditions in respiratory exchange ratio. These data suggest that caffeine may play an ergogenic role in exercise performance by altering both neural perception of effort and substrate availability.