It is well established that in human subjects a proportion of urea production undergoes hydrolysis in the gastrointestinal tract with release of N potentially available for amino acid synthesis. Previous studies have suggested adaptive changes in urea kinetics, with more urea-N retained within the metabolic pool during reduced dietary intakes of energy and protein. We therefore investigated the effect of rate and extent of weight loss on adaptive changes in urea kinetics in two groups (each n 6) of obese men (mean age 43 (sd 12) years, BMI 34·8 (sd 2·9)kg/m2) during either total starvation for 6d or a very-low-energy diet (2·55MJ/d) for 21d. Subjects were resident in the Human Nutrition Unit of the Rowett Research Institute (Aberdeen, Scotland, UK) and lost 6 and 9% initial body weight within the starvation and dieting groups respectively. Changes in urea-N metabolism were assessed by stable isotope tracer kinetics using [15N15N]urea infused intravenously for 36h before, during and after weight loss. In response to weight loss, urea production decreased (P<0·01) by 25% from 278 to 206μmol urea-N/h per kg within the dieting group only. However, no changes were observed in the proportion of urea being hydrolysed in the gastrointestinal tract (range 20–25%) or in the proportion of N retained for anabolic purposes (80–85% urea-N from gastrointestinal hydrolysis) within either group. It was concluded that no adaptive changes in urea kinetics occurred in response to either the different rate or extent of weight loss.