1. The response of the plasma concentration of urea to the oral and intravenous administration of alanine was studied in healthy adult humans.

2. The instantaneous rate of urea synthesis was calculated by using a model-dependent procedure. The errors in this procedure were calculated and it was shown that analytical precision and sampling frequency, and the estimates of the distribution volume and elimination fluxes, were adequate to determine the synthesis parameters.

3. A direct test of the compartmental model was made by the intravenous injection of exogenous urea. The one-compartment model with first-order elimination gave a good fit to the experimental results at times greater than 8 min after the injection.

4. Both oral and intravenous loads of alanine had dose-dependent effects on the rate of urea synthesis. There was no evidence of a limit to the maximum possible rate of urea synthesis in these experiments and the values obtained were similar to published results for different stimuli and methods of measurement.

5. The rate of synthesis increased more rapidly after intravenous loads and subjective side-effects were less severe. The intravenous administration of alanine appears to be a suitable stimulus for urea synthesis.

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