The effect of carbohydrate (CHO) ingestion on metabolic responses to exercise has been investigated. Subjects cycled at approximately 70% of maximal oxygen uptake to fatigue [135 +/- 17 (+/- SE) min] on the first occasion (control, CON) and at the same work load and duration on the second occasion but with addition of ingestion of CHO during the exercise. Biopsies were taken from the quadriceps femoris muscle before and after exercise. The sum of the hexose monophosphates (HMP), as well as lactate and alanine, in muscle was higher after CHO exercise (P less-than-or-equal-to 0.05, P less-than-or-equal-to 0.05, and P less-than-or-equal-to 0.01, respectively). Acetylcarnitine increased during exercise but was not significantly different between treatments after exercise (CON, 6.6 +/- 1.7; CHO, 10.0 +/- 1.2 mmol/kg dry wt; P = NS). The sum of the tricarboxylic acid cycle intermediates (TCAI; citrate + malate + fumarate) was increased during exercise and was higher after CHO exercise (2.34 +/- 0.32 vs. 1.68 +/- 0.17 mmol/kg dry wt; P less-than-or-equal-to 0.05). IMP was < 0.1 mmol/kg dry wt at rest and increased to 0.77 +/- 0.26 (CON) and 0.29 +/- 0.11 mmol/kg dry wt (CHO) (P less-than-or-equal-to 0.05) during exercise. It was recently found that during prolonged exercise there is initially a rapid and large expansion of TCAI and glycogenolytic intermediates in human muscle followed by a continuous decline in TCAI and glycogenolytic intermediates [K. Sahlin, A. Katz, and S. Broberg. Am. J. Physiol. 259 (Cell Physiol. 28): C834-C841, 1990]. Therefore, the present data indicate that administration of exogenous CHO attenuates reversal of TCAI. Presumably this is achieved by increasing the availability of HMP for glycolysis. These effects of CHO supplementation are achieved at lower levels of physiological stress, as evidenced by an attenuated IMP accumulation during the CHO experiment.