Several studies have found that caffeine improved endurance exercise performance, but the factors which are responsible for this are not fully understood. Possibilities include an increased free fatty acid (FFA) oxidation and a resultant sparing of muscle glycogen as well as an enhancement of neuromuscular function during exercise. In order to further examine these factors, six varsity level runners (&OV0312;O2max= 63.3 ml·kg−1·min−1) were studied over 90 min of treadmill running (70% &OV0312;O2max) in a thermoneutral environment in order to determine the metabolic and neuromuscular effects of caffeine (6 mg·kg−1) administered in a randomized, crossover, double-blind manner. Subjects were habitual caffeine consumers (200 mg·d−1) and were given identical diets during each 3-d testing period. Caffeine administration, 60 min prior to exercise, significantly (P< 0.05) increased plasma FFA levels both prior to and during exercise. Caffeine administration did not alter any of the other variables examined: &OV0312;O2, HR, RER, rating of perceived exertion; plasma levels of glucose, lactate, epinephrine, and norepinephrine; or neuromuscular function (maximal voluntary strength, peak twitch torque, and motor unit activation). We conclude that caffeine administration (6 mg·kg−1) in athletic, habitual caffeine consumers increased plasma FFA levels but had neither metabolic nor neuromuscular effects that would be of potential ergogenic benefit in endurance running.