The aim of this study was to evaluate the use of the [14C]-sodium bicarbonate/urea technique to measure the change in total energy expenditure after weight loss and a period of weight maintenance. Eleven healthy subjects (6 men and 5 women aged 50 +/- 3 yrs, BMI 34.1 +/-2.1 kg/ m2, body fat 38.7 +/-3%) underwent 8 weeks of energy restriction using a combination of "Modifast" formula and one small meal per day (approximately 3.3 MJ/day). For an additional 2 weeks, subjects resumed a solid food diet that contained enough energy to stabilize body weight at the newly reduced level. Body composition, total energy expenditure (TEE), resting energy expenditure (REE) and the thermic effect of a 2.7 MJ test meal (TEF) were measured at both weeks 0 and 10. At week 10 as compared to week 0, body weight decreased by 12.2+/-1.6 kg (12.5%)(P<0.001). Total fat and lean mass decreased by 8.4+/-1.0 kg (20.4%) and 3.8+/-0.7 kg (6.7%), respectively (P< 0.001). REE decreased by 500+/-128 kJ/day (5.6+/-1.3%)(P<0.002). Decreases in the TEE (0.18 +/-;3.7%)and TEF(1.4+/-0.9%) were not significant. In conclusion, although [14C]-sodium bicarbonate/urea was well tolerated and did not interfere with normal daily activities, it did not have sufficient sensitivity to accurately measure weight loss induced changes in TEE in the range of 0.1-10%.