Isolated, superfused, field stimulated guinea-pig vas deferens, in which the noradrenaline stores had been labelled by preincubation with tritiated (-)-noradrenaline, was used to study the interaction between exogenous and endogenous acetylcholine and adrenergic neuroeffector function. Exogenous acetylcholine was found to exert a dual muscarinic effect on the preparation, consisting of depression of the secretion of tracer noradrenaline from the sympathetic nerves, as well as enhancement of the nerve stimulation-induced contraction of the preparation. The results indicate that endogenous acetylcholine may play an analogous role, since eserine enhanced the nerve stimulation-induced contraction, without markedly affecting the secretion of labelled noradrenaline (the effect was abolished by atropine), while higher concentrations of atropine depressed the contraction and actually enhanced the secretion of labelled noradrenaline. The findings support the concept that guinea-pig vas deferens has a dual, cholinergic as well as adrenergic, innervation, and that the cholinergic nerves exert a dual modulatory effect on sympathetic neuro-effector function in this tissue: Firstly they appear to restrict the secretion of sympathetic neurotransmitter (via pre-junctional muscarinic receptors, on the adrenergic nerve terminals), and secondly they seem to enhance the excitability of the smooth muscle to sympathetic neurotransmitter (via post-junctional muscarinic receptors, on the smooth muscle cells).