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The purpose of this study was to investigate the ergogenic effect of oral inosine (IN) supplementation (6,000 mg.d-1 for 2 d) upon 3-mile run time (3MTIME) and VO2 peak. Nine highly trained endurance runners participated in a double-blind, placebo (PL), crossover study. Each subject undertook an IN or PL trial, consisting of three exercise tests: a submaximal warm-up run (SUBRUN), a competitive 3-mile treadmill run (3MRUN), and a maximal treadmill run (MAXRUN) to determine VO2 peak and time to exhaustion (MAXTIME). Additional measurements during the 3MRUN and MAXRUN included oxygen uptake (VO2), ventilation (VE), respiratory exchange ratio (R), and ratings of perceived exertion (RPE); blood samples were also taken prior (PRERUN) to the SUBRUN test and following the SUBRUN, 3MRUN, and MAXRUN tests in order to assess glucose, pyruvate, lactate, phosphorus, 2,3-DPG, hemoglobin, and uric acid. Analyses of the data revealed no significant effect of oral IN supplementation either upon 3MTIME (IN = 18.31 +/- 1.21; PL = 18.33 +/- 1.15 min) or VO2 peak (IN = 58.6 +/- 5.1; PL = 60.7 +/- 4.5 ml O2.kg-1.min-1) or upon other dependent variables. MAXTIME was significantly longer during the PL trial (P less than 0.05), suggestive of a possible impairment effect of oral IN supplementation. Based upon our data, we conclude that IN is not an effective ergogenic aid to enhance athletic performance of an aerobic nature.