The uptake of noradrenaline by the isolated perfused rat heart was studied after perfusion with a medium containing various concentrations of (+/-)-[(3)H]-noradrenaline. Simultaneous measurement of the uptake of [(3)H]-noradrenaline and of the net increase in the noradrenaline content of the heart showed that [(3)H]-noradrenaline entering the heart both increased the tissue content and exchanged with endogenous noradrenaline. A large part (about 75%) of the endogenous noradrenaline pool, however, exchanged very slowly if at all with exogenous noradrenaline. The initial rates of noradrenaline uptake satisfied Michaelis-Menten kinetics with a Km for (+/-)-noradrenaline of 6.64x10(-7) M. Further analysis of the uptake process indicated that noradrenaline entered into at least two intracellular pools at different rates. Measurement of the initial rates of noradrenaline uptake during perfusion with various concentrations of nonradioactive (+)- and (-)-noradrenaline showed that the uptake process exhibited stereochemical specificity. The Km values for (+)- and (-)-noradrenaline were 13.9x10(-7) and 2.66x10(-7) M respectively. Cocaine acted as a potent competitive inhibitor of noradrenaline uptake. This finding suggested that diffusion did not play any significant role in the entry of noradrenaline into the tissue.