This study has tested the hypothesis that nicotine might increase thermogenesis in rats by activating the sympathetic nervous system which supplies brown adipose tissue. Three hours after a single injection of nicotine, both the turnover of norepinephrine and the binding of the purine nucleotide, guanosine 5'-diphosphate (GDP) to mitochondria from brown adipose tissue were significantly increased. After 11 days of treatment with nicotine, the turnover of norepinephrine and the GDP binding to mitochondria from brown adipose tissue both remained elevated but weight gain was not different. These data are consistent with the hypothesis that nicotine may have part of its effect through changes in thermogenesis involving sympathetic nervous activation of peripheral thermogenic tissues such as brown adipose tissue.