The present study examines the independent effects of amino acids and leucine in modulating insulin's effect on leucine kinetics in 24-h fasted conscious dogs during an experimental period where insulin was infused at 600 mU.kg-1.h-1. Group I (n = 7) received saline, group II (n = 10) received sequential infusions of L-leucine at 0, 1, 3, and 1 mumol.kg-1.min-1 each lasting for 90 min, and group III (n = 6) received L-amino acids with doses of L-leucine matching those of group II. Plasma leucine (mumol/l) was 120 +/- 5 basally and 135 +/- 23 and 129 +/- 12 during the infusion of 3.0 mumol.kg-1.min-1 in groups II and III compared with 40 +/- 3 in group I. Leucine rate of appearance (mumol.kg-1.min-1) was 3.5 +/- 0.3 during the basal period and was suppressed 80% in both groups II and III as compared with 40% in group I (P less than 0.01). Leucine oxidation (basal = 0.7 +/- 0.15 mumol.kg-1.min-1) dropped 20% in group I but increased to threefold basal in group II and twofold in group III (P less than 0.05). Nonoxidative rate of disposal (basal = 2.6 +/- 0.2 mumol.kg-1.min-1) dropped 25% in group I and 55% in group II but did not change in group III. These data show that, in addition to insulin, amino acids and particularly leucine cause a marked suppression of proteolysis. Availability of all amino acids to prevent hypoaminoacidemia is necessary to sustain basal rates of protein synthesis. The infusion of leucine alone resulted in significant stimulation of leucine oxidation.