The aim of this study was to determine the site and mechanism of action of nicotine on sympathetic neuroeffector transmission in the isolated pulmonary artery of the rabbit. Nicotine and cocaine potentiated the constrictor response elicited by electrical-field stimulation of postganglionic adrenergic neurones. The potentiation was reversible and in the case of nicotine, no tachyphylaxis developed. The nicotine-induced potentiation was characterized by a rapid onset and an initial, transitory peak, while the enhancement caused by cocaine progressed more slowly and was monophasic. Hexamethonium and (+)-tubocurarine prevented the potentiation caused by nicotine. Nicotine did not prevent the adrenergic neurone blocking effect of bretylium on the response to field stimulation. Nicotine increased the stimulation-induced outflow of tritium from pulmonary artery preloaded with 3H-(--)-noradrenaline. Contractions of the artery elicited by tyramine were enhanced by pargyline, unaltered by nicotine and blocked by cocaine. Nicotine did not alter the concentration--response curve of exogenous (--)-noradrenaline while cocaine moved it to the left. The accumulation of 3H-(--)-noradrenaline by rabbit isolated aorta was not altered by nicotine, hexamethonium and (+)-tubocurarine. The accumulation of 3H-nicotine by the aorta was much lower than that seen with 3H-(--)-noradrenaline. The disposition of the 3H-nicotine accumulation into adventitia and media was concentration-independent. These results suggest (1) that nicotine potentiates the neurogenic vasoconstriction response in part by increasing the stimulation-induced release of transmitter from adrenergic neurone terminals; (2) that the site of the nicotinic receptors mediating this action is located on the outer surface of the neurones; and (3) that the potentiation is not due to blockade of noradrenaline re-uptake.