Fat feeding stimulates sympathetic nervous system (SNS) activity in rats. To determine if fats vary in their potency as stimulants of the SNS, [³H]norepinephrine ([³H]NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of animals fed lab chow diets supplemented with safflower oil, coconut oil, or medium-chain triglycerides (MCT). At 5 days, all three fats accelerated [³H]NE turnover in heart and did so equally, but only when the fat supplement represented an increase in energy intake. However, after 14 days, safflower oil and coconut oil but not MCT increased [³H]NE turnover in heart compared with turnover rates obtained in animals fed isoenergetic amounts of chow. Furthermore, the stimulatory effect of safflower oil on [³H]NE turnover was statistically greater than that seen in animals fed equivalent amounts of coconut oil. In vivo synthesis of NE assessed by accumulation of dopamine (DA) in heart following inhibition of dopamine-β-hydroxylase (DβH) was likewise highest in safflower oil-fed rats and lowest in those fed MCT. Thus, sympathetic activation by dietary fat varies among different fats, suggesting a role for fatty acid intake in dietary regulation of the SNS.