This study examined the effect of ingesting caffeine (6 mg kg-1) on muscle carbohydrate and fat metabolism during steady-state exercise in humans. Young male subjects (n = 10) performed 1 h of exercise (70% maximal oxygen consumption (VO2,max)) on two occasions (after ingestion of placebo and caffeine) and leg metabolism was quantified by the combination of direct Fick measures and muscle biopsies. Following caffeine ingestion serum fatty acid and glycerol concentration increased (P< or =0.05) at rest, suggesting enhanced adipose tissue lipolysis. In addition circulating adrenaline concentration was increased (P< or =0.05) at rest following caffeine ingestion and this, as well as leg noradrenaline spillover, was elevated (P< or =0.05) above placebo values during exercise. Caffeine resulted in a modest increase (P< or =0.05) in leg vascular resistance, but no difference was found in leg blood flow. Arterial lactate and glucose concentrations were increased (P< or =0.05) by caffeine, while the rise in plasma potassium was dampened (P< or =0.05). There were no differences in respiratory exchange ratio or in leg glucose uptake, net muscle glycogenolysis, leg lactate release or muscle lactate, or glucose 6-phosphate concentration. Similarly there were no differences between treatments in leg fatty acid uptake, glycerol release or muscle acetyl CoA concentration. These findings indicate that caffeine ingestion stimulated the sympathetic nervous system but did not alter the carbohydrate or fat metabolism in the monitored leg. Other tissues must have been involved in the changes in circulating potassium, fatty acids, glucose and lactate.