The effect of caffeine on the resting metabolic rate (RMR) was investigated in endurance exercise-trained (N = 14) and inactive (N = 10) male individuals. Subjects were also classified into regular and non-regular consumers of caffeine. After an overnight fast, RMR was measured using an indirect calorimetry open circuit system. Thereafter, subjects orally consumed 300 mg of caffeine, after which RMR was measured for 90 min. Five of the exercise-trained subjects were also studied after the administration of a placebo. Plasma concentrations of glycerol and free fatty acid and respiratory exchange ratio (R) were measured at each 15-min interval. Before caffeine ingestion, no significant differences were observed in RMR, R, glycerol, free fatty acid and blood pressure levels between exercise-trained and inactive groups. Following caffeine consumption, a three-way analysis of variance revealed that inactive subjects exhibited a greater increase (P less than 0.05) in RMR than did exercise-trained subjects. No significant differences were observed in RMR response between regular or nonregular consumers of caffeine. Moreover, no differences were observed in glycerol, free fatty acid, heart rate, and blood pressure response between exercise-trained and inactive subjects and between regular and non-regular consumers of caffeine. These results suggest that endurance training results in a reduced thermogenic response to a caffeine challenge.