Previously it has been shown that radiolabelled histamine is taken up by brain slices and may subsequently be released by depolarizing stimuli in a calcium-dependent manner, indicating the involvement of neurons in uptake and release of histamine. The present study demonstrates that after incubation of brain slices with low (nM) concentrations of [(3)H]histamine the amine may be taken up by (and released from) dopaminergic and serotonergic neurons (nerve terminals). Thus 6-hydroxydopamine- and 5,7-dihydroxytryptamine-induced lesions not only reduced the uptake of [(3)H]dopamine (in striatal slices) and [(3)H]serotonin (in hippocampal slices), but also, though to a lesser extent, that of [(3)H]histamine. Immunocytochemical findings revealed that the neurotoxins did not visibly affect histaminergic neurons. Lesioning of noradrenergic neurons appeared not to alter significantly the uptake of [(3)H]histamine. Further, various drugs acting on either catecholamine-, serotonin- or opioid-receptors and known to cause presynaptic inhibition of the release of [(3)H]dopamine or [(3)H]wrotonin from striatal or hippocampal slices also inhibited [(3)H]histamine release. It is concluded that incubation of brain slices with low concentrations of [(3)H]histamine does not result in a selective labelling of histaminergic neurons. The possibility that, unlike other monoamines, histamine is not subject to high-affinity uptake by the nerve terminals from which it was released, is discussed.