A study was designed to compare the effects, in vitro, of insulin-like growth factor-1 (IGF-1) and insulin on rat epitrochlearis muscle metabolism during aging (1, 6-8, or 18-20 months). Our results showed that in young epitrochlearis, IGF-1 was equipotent to insulin in stimulating 2-deoxy-glucose and aminoisobutyric acid transport but more potent in increasing tyrosine incorporation into protein. Both insulin and IGF-1 action on glucose transport was decreased in adult compared with young muscle. Whereas an insulin resistance of amino acid transport and protein synthesis was also recorded in adult rat muscle, the stimulatory effect of IGF-1 on these processes was abolished. Thus the degree of resistance observed varied both with the agonist and with the subsequent metabolic process observed. Whereas modifications of IGF-1 action in mature animals may be correlated in part to the dramatic decrease of IGF-1 receptors (80%), no similar observations were recorded for the insulin receptor. Since muscle IGF-1 receptor gene expression did not decrease in parallel with receptor number, an alteration in IGF-1 receptor messenger RNA (mRNA) translation or receptor degradation may be hypothetized. We concluded that: 1) In contrast to glucose transport, intracellular IGF-1 and insulin postreceptor pathways leading to amino acid uptake and protein metabolism differ. 2) Modification in postbinding events might be involved in decreased insulin- and IGF-1-stimulated muscle metabolism during aging.