T he mRNA levels for the mitochondrial uncoupling protein (UCP1) in fat tissues of A/J and C57BL/6J inbred strains of mice varied in a regional-specific manner after stimulation of adrenergic signaling by cold exposure or treatment with a beta3-adrenergic agonist. While the differences between strains were minimal in interscapular brown fat, large differences occurred in white fat tissues, particularly in retroperitoneal fat. Among the AXB recombinant inbred strains, the Ucp1 mRNA levels varied up to 130-fold. This large induction at the mRNA level was accompanied by a corresponding increase in brown adipocytes as revealed by immunohistology with anti-UCP1 antibodies. A high capacity to induce brown fat in areas of traditional white fat had no impact on the ability to gain weight in response to high fat and sucrose diets, but did correlate with the loss of weight in response to treatment with a beta3-adrenergic agonist (CL 316,243). This genetic variation in mice provides an experimental approach to identify genes controlling the induction of brown adipocytes in white fat tissues.