Clinical case reports have documented disturbances of carbohydrate and lipid metabolism in aromatase deficient and estrogen resistant males. The aim of the present study was to explore the metabolic functions of estrogens in male mice and to dissect the estrogen receptor (ER) specificity of such effects. Total body fat content and serum levels of leptin were followed in ER alpha knockout (ERKO), ER beta knockout (BERKO), and ER alpha/beta double knockout (DERKO) mice. Neither the total body fat nor serum leptin levels were altered in any group before or during sexual maturation. However, after sexual maturation ERKO and DERKO, but not BERKO, demonstrated a clear increase in total body fat and enhanced serum leptin levels. Serum cholesterol was increased and a qualitative change in the Lipoprotein profile, including smaller LDL particles, was observed in ERKO and DERKO mice. In conclusion, ER alpha but not ER beta -inactivated male mice develop obesity after sexual maturation.