Purpose: This study was:designed to test the hypothesis that combined administration of propranolol and caffeine (Pr+C) would increase endurance performance compared with the administration of propranolol alone (Pr) if caffeine would be able to increase plasma free fatty acid (FFA) availability and/or lower plasma potassium concentration compared with propranolol administration alone. Methods: Fifteen volunteers participated in the double-blind placebo-controlled randomized cross-over study. An endurance exercise rest until: exhaustion was performed after ingestion of placebo (Pl), 80-mg propranolol (Pr), and 80-mg propranolol plus 5 mg kg(-1) caffeine (Pr+C). Results: Endurance lime (+/-SD) was 79.3 +/- 20.4 min in the Pl trial, 22.6 +/- 10.8 min in the Pr trial and 31.2 +/- 17.2 min in the Pr+C mal (P <0.001). The difference between the Pr and Pr+C trials just failed to reach statistical significance (P = 0.056). Plasma FFA concentration and plasma potassium concentrations were similar in the Pr and Pr+C trials, but differed significantly from: the Pl trial (P <0.05), Conclusion: Although there was a clear tendency for an improved performance in the Pr+C trial compared to the Pr trial, this improvement was not associated with increased plasma FFA concentration and/or reduced plasma potassium concentration in the Prl-C compared to the Pr trial. These results do not support the hypothesis that caffeine improves endurance performance by stimulating lipolysis or lowering plasma potassium concentration.