Interpretation of tracer studies of amino acid kinetics in the fed state is dependent on knowledge of splanchnic uptake of diet-derived amino acids. We studied five healthy control children and five children with cystic fibrosis (CF). After an overnight fast, the children ingested, hourly, a formula diet for 11 h. 5,5,5-[2H3]Leucine was added to the feedings during the last 6 h, and an i.v. infusion of 1-[13C]leucine was administered during the last 2 h of the formula feeding. The mean rate of splanchnic uptake of leucine was similar in the CF and control group, 23.8 +/- 24.0 and 21.5 +/- 21.2 mumol.kg-1.h-1, respectively. Fractional splanchnic uptake of leucine was not significantly different in the patients with CF (0.16 +/- 0.112 mean +/- SD) compared with the control children (0.244 +/- 0.256(-1)). The rate of whole body protein breakdown was not significantly different between the groups (CF versus control) with (159 +/- 18 versus 135 +/- 28 mumol.kg-1.h-1) or without (135 +/- 14 versus 114 +/- 20 mumol.kg-1.h-1) correction for splanchnic leucine uptake. However, for the 10 cases combined, protein breakdown corrected for splanchnic leucine uptake (147 +/- 26 mumol.kg-1.h-1) was 18% greater than uncorrected protein breakdown (124 +/- 20 mumol.kg-1.h-1) (p = 0.009). The data suggest that companion studies of splanchnic uptake might enhance the interpretation of leucine kinetics in the fed state.