The effect of noradrenaline (NA) on acetylcholine (ACh) release from guinea-pig brain was investigated in superfused cerebral cortex slices and in unrestrained unanaesthetized animals provided with epidural cups. The amine reduced the ACh release from electrically stimulated tissue and its effect was antagonized by phentolamine and phenoxybenzamine, but not by propranolol and spiroperidol. The injection of NA (150 microgram) into the cerebral ventricles caused sedation, E.Co.G. synchronization and reduced ACh outflow from the parietal cortex. This inhibition was counteracted by alpha-blocking agents. A lower dose of NA (50 microgram) did not change the behaviour, but produced a late increase in ACh outflow, prevented by spiroperidol. These results fit well with the hypothesis that NA restrains, via alpha-receptors, the ACh secretion from the nerve endings and indirectly support the view that the amine reduces the firing rate of the corticopetal cholinergic neurones. The late increase in ACh outflow, observed in vivo, may be referred to secondary activation of the dopaminergic neurones, known to enhance the cortical ACh release in this animal species.