OBJECTIVE: To investigate the impact of beta-adrenoceptor deficiency on the metabolic effects of leptin. MEASUREMENTS: Leptin was infused subcutaneously through an osmotic minipump in wild-type (WT) and beta(1)/beta(2)/beta(3)-adrenoceptor knockout (beta-less) mice and its effects on food intake, energy expenditure, carbohydrate and lipid utilization as well as on the levels of expression of the brown adipose tissue (BAT), thermogenic marker uncoupling protein-1 (UCP1) and type II deiodinase (D2) mRNAs were compared. RESULTS: Leptin treatment decreased food intake by 23% in both the WT and the beta-less mice. In pair-fed animals being used as controls, leptin treatment was found to increase energy expenditure in WT, but not in beta-less mice. No difference was observed in carbohydrate or fat utilization between leptin-treated WT and beta-less mice. Leptin increased UCP1 and D2 mRNA levels in WT mouse BAT 1.7- and 3-fold, respectively, but had no effect on the expression of these genes in beta-less mouse BAT. CONCLUSION: The stimulatory effects of leptin on oxygen consumption, BAT UCP1 and D2 expression require functional beta-adrenoceptors, but its inhibitory effect on food intake and its stimulatory effect on fat utilization is independent of the beta-adrenoceptor signalling.