The aim of this study was to determine the effects of caffeine ingestion on estimated substrate utilisation during treadmill running at an initial level of 70%-75% of maximal oxygen consumption after which subjects ran to exhaustion. Twelve subjects undertook either a control, placebo, a small (10 mg X kg-1) or a large (15 mg X kg-1) dose of caffeine in a double-blind design to determine whether caffeine affected the substrate usage during running. Venous blood was collected prior to and during the experimental runs and was later analysed for free fatty acids (FFA), glycerol, triglycerides, lactate and glucose concentrations. The results of this experiment suggest that maximal running performance can be increased by large doses of caffeine. Furthermore, the subjects' respiratory exchange ratios were lower and FFA concentrations were higher following the ingestion of large amounts of caffeine than during other trials, suggesting that a larger proportion of energy was derived from fat being used preferentially during the trial following ingestion of this large dose of caffeine. The subjects rating of perceived exertion (RPE) were lower following the ingestion of a large dose of caffeine than it was in any of the other trials. This study differs from others in this area in so much that caffeine has been found to have positive effects during maximal running when used in large doses.