(-)-N-(2-Chloroethyl)-norapomorphine [-)-NCA) inhibited in a concentration-dependent manner the electrically evoked [3H]acetylcholine release in slices of cat caudate. The inhibition by (-)-NCA was reversible and antagonized by the benzamide neuroleptic S-sulpiride. Although (-)-NCA is an irreversible antagonist at some behaviorally relevant postsynaptic dopamine receptors, its effect as an agonist on dopamine receptors modulating [3H]acetylcholine release strongly resembles its action on presynaptic dopamine autoreceptors modulating [3H]dopamine release. Our results suggest that the dopamine receptor modulating [3H]acetylcholine release may not be an appropriate in vitro model for those behaviorally relevant postsynaptic dopamine receptors which are antagonized by (-)-NCA. It is more likely that it conforms to the characteristics of presynaptic release-modulating dopamine autoreceptors. The agonistic action of (-)-NCA at presynaptic dopamine receptors, in contrast to the irreversible antagonism of some postsynaptic dopamine receptors by (-)-NCA, should be interpreted with caution. Evidence is presented which suggests that (-)-NCA breaks down in solution into (-)-N-(2-hydroxylethyl)-norapomorphine [-)-NHA). Since (-)-NHA is an agonist at presynaptic dopamine receptors, this physicochemical breakdown product may be partly responsible for the apparent agonistic properties of (-)-NCA under our in vitro conditions.