1. The influence on leucine disposal of physiological alterations in plasma insulin concentrations was examined in three groups of healthy male subjects, six in each group. After an overnight fast the subjects received an intravenous infusion of either leucine (300 μmol/min for 150 min, series A), or leucine plus glucose (2.2 mmol/min, series B), or leucine, somatostatin (7 μg/min) and glucagon (1 ng/min, series C). Arterial concentrations of substrates and their net exchange across the splanchnic and leg tissues were determined with a catheter technique. 2. Insulin concentrations rose from 12 ± 2 to 20–22 μ-units/ml in series A, from 11 ± 3 to 60–65 μ-units/ml in series B and decreased from 8 ± 1 to approximately 5 μ-units/ml in series C. 3. The basal leucine concentration for all subjects was 109 ± 8 μmol/l and it rose progressively during the infusions. In series A, the level was 598 ±20 μmol/l after 150 min. The corresponding value was 542 ±38 μmol/l in series B and 651 ±25 μmol/l in series C. Significant differences were observed between series A and B ( P < 0.05) and series A and C ( P < 0.01) when data for 90–150 min of infusion were combined (analysis of variance). 4. In all groups the leucine infusion resulted in an augmented net uptake of leucine across the leg (77-85 μmol/min) and across the splanchnic bed (61-72 μmol/min) but no significant inter-group differences were observed. 5. From these findings we conclude that insulin accelerates and hypoinsulinaemia slows the disposal of an exogenous load of leucine. These effects of insulin result in only modest differences in arterial leucine concentrations and in no demonstrable changes in peripheral or splanchnic leucine exchange, suggesting that insulin plays only a minor role in the disposal of leucine.