To test the hypothesis that marathon running is dependent on lipid oxidation, 12 post-absorptive males (31.9 +/- 2.1 yr) ran a treadmill marathon and substrate utilization was assessed. Subjects were placed into a fast (F < or = 2 hr, 45 min; 73.3% VO2max), or a slow (S < or = 3 hr, 45 min; 64.5% VO2max) marathon group. The day before testing subjects rested, but ate their normal diet. Subjects were tested in the morning after an overnight fast, and only tap water, at a rate of 1 l.h, was ingested during exercise. Blood glucose concentration rose at exercise onset, peaked at approximately an hour, but then decreased over time remaining at or above resting levels. Free fatty acids and glycerol rose continuously. No significant differences in plasma FFA, glycerol, or blood glucose concentrations were observed between F or S groups during the marathon. Mean blood lactate concentration was significantly higher (P < 0.05) in the F (2.1 +/- 0.3 mM) group than the S (1.2 +/- 0.2 mM) during exercise. Mean plasma epinephrine was significantly higher in the F (0.9 +/- 0.2 ng.ml-1) than the S (0.6 +/- 0.2 ng.ml-1) group; norepinephrine was also higher in F (3.9 +/- 1.4 ng.ml-1) than the S (2.5 +/- 0.9 ng.ml-1, P < or = 0.05). Blood lactate and epinephrine concentrations correlated significantly (4r = 0.76 and 0.78 in F and S groups, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)