We have determined the individual and combined effects of insulin and prior exercise on leg muscle protein synthesis and degradation, amino acid transport, glucose uptake, and alanine metabolism. Normal volunteers were studied in the postabsorptive state at rest and about 3 h after a heavy leg resistance exercise routine. The leg arteriovenous balance technique was used in combination with stable isotopic tracers of amino acids and biopsies of the vastus lateralis muscle. Insulin was infused into a femoral artery to increase the leg insulin concentrations to high physiologic levels without substantively affecting the whole-body level. Protein synthesis and degradation were determined as rates of intramuscular phenylalanine utilization and appearance, and muscle fractional synthetic rate (FSR) was also determined. Leg blood flow was greater after exercise than at rest (P<0.05). Insulin accelerated blood flow at rest but not after exercise (P<0.05). The rates of protein synthesis and degradation were greater during the postexercise recovery (65+/-10 and 74+/-10 nmol x min(-1) x 100 ml(-1) leg volume, respectively) than at rest (30+/-7 and 46+/-8 nmol x min(-1) x 100 ml(-1) leg volume, respectively; P<0.05). Insulin infusion increased protein synthesis at rest (51+/-4 nmol x min(-1) x 100 ml(-1) leg volume) but not during the postexercise recovery (64+/-9 nmol x min(-1) x 100 ml(-1) leg volume; P<0.05). Insulin infusion at rest did not change the rate of protein degradation (48+/-3 nmol x min(-1) 100 ml(-1) leg volume). In contrast, insulin infusion after exercise significantly decreased the rate of protein degradation (52+/-9 nmol x min(-1) x 100 ml(-1) leg volume). The insulin stimulatory effects on inward alanine transport and glucose uptake were three times greater during the postexercise recovery than at rest (P<0.05). In contrast, the insulin effects on phenylalanine, leucine, and lysine transport were similar at rest and after exercise. In conclusion, the ability of insulin to stimulate glucose uptake and alanine transport and to suppress protein degradation in skeletal muscle is increased after resistance exercise. Decreased amino acid availability may limit the stimulatory effect of insulin on muscle protein synthesis after exercise.