21 patients undergoing major abdominal surgery were randomly assigned to one of three groups. On the day of surgery and for the succeeding 4 days each group received a daily infusion of one of the following: 10 g glucose plus 70 mmol NaHCO3, 70 mmol leucine plus 70 mmol NaHCO3, or 70 mmol of sodium alpha-ketoisocaproate (KIC). No other calories were given. Leucine infusions had no significant effect on nitrogen (N) balance, 3-methylhistidine excretion, or plasma concentrations of pre-albumin or retinol-binding protein, but they increased blood acetoacetate concentration (p = 0.004). N balance was less negative (p = 0.002) and 3-methylhistidine excretion lower (p = 0.002) in the group receiving KIC than in those receiving glucose. Blood ketone bodies, plasma prealbumin, and plasma retinol-binding protein concentrations at the end of the study were significantly higher in the KIC group than in the others. These N-sparing effects of KIC may be related to the heightened ketosis that followed its administration, to suppression of protein degradation, or to an effect on liver protein turnover. KIC alone in small doses diminishes N wastage in postoperative but under the same conditions leucine does not.