We tested the hypothesis that regular endurance exercise prevents the age-related decline in insulin action typically observed in healthy, sedentary adults. An index of whole body insulin sensitivity (ISI), obtained from minimal model analysis of insulin and glucose concentrations during a frequently sampled intravenous glucose tolerance test, was determined in 126 healthy adults: 25 young [27 +/- 1 (SE) yr; 13 men/12 women] and 43 older (59 +/- 1 yr; 20/13) sedentary and 25 young (29 +/- 1 yr; 12/13) and 33 older (60 +/- 1 yr; 20/13) endurance trained. ISI values were lower in the older vs. young adults in both sedentary (-53%; 3.9 +/- 0.3 vs. 7.0 +/- 0.7 x10(-4) x min(-1) x microU(-1) x ml(-1); P < 0.01) and endurance-trained (-36%; 7.9 +/- 0.6 vs. 12.4 +/- 1.0 x 10(-4) min(-1) x microU(-1) x ml(-1); P < 0.01) groups, but the value was 72-102% higher in the trained subjects at either age (P < 0.01). In subgroup analysis of sedentary and endurance-trained adults with similar body fat levels (n = 62), the age-related reduction in ISI persisted only in the endurance-trained subjects (12.9 +/- 1.9 vs. 8.7 +/- 1.2 x 10(-4) x min(-1) x microU(-1) x ml(-1); P < 0.01). The results of the present study suggest that habitual endurance exercise does not prevent the age-associated decline insulin action. Moreover, the age-related reduction in ISI in endurance-trained adults appears to be independent of adiposity.