The sympathetic neurotransmitter norepinephrine interacts with both α- and α-adrenergic receptors to dramatically stimulate the rate of substrate oxidation and thermogenesis in brown adipocytes. Accompanying this norepinephrine-induced metabolic stimulation are complex changes in cation fluxes across the plasma membrane which appear to reflect altered movement through channels as well as altered membrane transport processes. Norepinephrine activation of brown adipocytes is accompanied by a net efflux of protons from the cells. Isolated hamster brown adipocytes responded robustly to maximal levels of norepinephrine, increasing their heat production almost twenty-fold. Maximal concentrations of phenylephrine and isoproternol also stimulated brown adipocyte respiration, the latter having a much greater effect than the former. Although amiloride significantly lowered the phenylephrine stimulation by 64%, it did not significantly reduce the thermogenic effect of isoproternol. There are a variety of mechanisms whereby norepinephrine could stimulate the antiport system.