The influence exerted by monoamines on acetylcholine release was studied in electrically stimulated slices of guinea pig nucleus basalis magnocellularis (nbM) prelabelled with 3H-choline (3H-Ch). Noradrenaline, 30 microM, and clonidine, 1 microM, reduced the evoked 3H-Ch efflux by about 50%, but phenylephrine, 100 microM, did not; idazoxan, 0.1 microM, but not prazosin, 1 microM, antagonized these effects, pointing to the involvement of alpha 2 receptors. Apomorphine, 1 or 30 microM, reduced 3H-Ch efflux from nbM slices as well. The effect was shared by quinpirole, 1 or 10 microM, but not by 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (SKF 38393), 10 microM, and was antagonized by sulpiride, 1 microM, but not by R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin++ +-7-ol (SCH 23390), 1 microM, suggesting the involvement of the D2 receptor subtype. 5-hydroxytryptamine (5-HT) 0.3-30 microM, and alpha-methyl-5-HT, 10 microM, significantly increased 3H-Ch efflux from nbM slices; the 5-HT2 antagonist ritanserin, 1 microM, prevented this response. 2-methyl-5-HT, 1-30 microM, inhibited the evoked 3H-Ch efflux and its effect was prevented by the 5-HT3 antagonist 1 alpha H,3 alpha,5 alpha H-tropan-3-yl-3,5-dichlorobenzoate (MDL 72222), 1 microM. These findings indicate that i) catecholamines inhibit nbM neurons through alpha 2 and D2 receptors and that ii) a complex serotonergic modulation of cholinergic function exists in the nbM, involving the activation of various receptor subtypes, which can mediate opposite responses.