The effects of histamine antagonists on noradrenaline-stimulated metabolic rate, tissue blood flow (estimated from the distribution of radiolabelled microspheres) and brown adipose tissue (BAT) oxygen extraction were studied in male anaesthetised rats. Injection of cimetidine (H2-receptor antagonist), reduced the noradrenaline-stimulation of metabolic rate and the increase in blood flow to BAT, but did not affect blood flow to white adipose tissue, skin, leg muscle, kidney, brain, or testes. Following noradrenaline, in vivo oxygen consumption of BAT, estimated from blood flow and oxygen extraction was depressed to 31% of control values by treatment with cimetidine, blood pressure was unaffected. Injection of the histamine (H1-receptor) antagonist, mepyramine, did not affect tissue blood flow or metabolic rate. In conscious animals, cimetidine did not affect resting oxygen consumption, but depressed the thermogenic responses to noradrenaline. These data suggest that the stimulation of BAT blood flow and thermogenesis by noradrenaline may be mediated in part by histamine acting on an H2-type receptor.