1. Groups of lean and genetically obese (ob/ob) mice were adapted to varying energy intakes and the rates of total protein turnover in liver, gut and kidney were measured.
2. Lean mice gained less weight when fed above maintenance and lost less weight when fed below maintenance than obese mice.
3. Hepatic protein turnover (mg/d) was sigmoidally related to digestible energy intake in lean mice but showed no significant changes with dietary intake in obese mice.
4. The changes in protein turnover resulted from changes in both the half-lives of protein synthesis and catabolism and in tissue protein content.
5. In the lean mice, protein turnover in kidney and gut was not significantly changed with increasing energy intake until the highest level was reached.
6. The findings suggest that protein turnover may be an important cycle for the regulation of energy balance in mice and that this cycle is impaired in the genetically obese (ob/ob) mice.