The effects of caffeine and ethanol on treadmill performance and metabolic responses to exercise were determined in four trained runners. Caffeine (2.5 mg.kg-1 body weight) or ethanol (25 ml) in 150 ml of grapefruit juice (total volume) or grapefruit juice (placebo) was randomly administered 10 minutes prior to and at 30 minutes of a 60 minutes treadmill run. The speed and grade of the treadmill was adjusted to elicit an average oxygen consumption of 80-85% of the subject's maximal oxygen consumption. All subjects completed the treadmill run for the caffeine and placebo conditions. Three of the four subjects could not complete the treadmill run following the second administration of ethanol. Exercise heart rate was significantly greater for the ethanol condition than for the placebo condition. Exercise oxygen consumption was greater following ethanol administration than for placebo, but the differences were not significant. Blood glucose rose significantly between 0 and 30 minutes of treadmill running for all three conditions. Between 30 minutes of treadmill running and either 60 minutes or the time of termination of the exercise, blood glucose decreased significantly by 24% following the second ethanol treatment. Plasma fatty acid, triglyceride, creatine phosphokinase, and renin contents followed expected exercise changes with a blunting of the rise of plasma fatty acids at 30 minutes of exercise for the ethanol condition. It was concluded that the administration of ethanol adversely influenced treadmill exercise performance by eliciting a hypoglycemic effect between 30 minutes and the termination of the exercise.