1. The effects of histamine on isolated goat middle cerebral artery were examined using two experimental approaches: recording of isometric tension and measurement of [3H]-noradrenaline efflux. 2. Cumulative addition of histamine (10(-7)-3 x 10(-2)M) and 2-pyridylethylamine (2-PEA, 10(-6)-3 x 10(-2)M) produced concentration-dependent contractile responses. Preincubation with diphenhydramine (10(-7), 10(-6)M) or cimetidine (10(-7), 10(-6)M) competitively inhibited the histamine-induced contractile response. 3. Endothelium denudation enhanced the contractile effects of histamine. 4. Transmural electrical stimulation elicited contractions which were enhanced by histamine (10(-7)M), 2-PEA (10(-6)M) and dimaprit (10(-4)M). Diphenhydramine (10(-5)M) inhibited the action of histamine, but cimetidine did not. 5. Noradrenaline (10(-8)-10(-4)M) elicited concentration-dependent contractions which were unaffected by histamine (10(-7)M). 6. In arteries preloaded with [3H]-noradrenaline, transmural electrical stimulation induced an increase in the tritium efflux, which was enhanced in the presence of histamine (10(-7)M). 7. Therefore, histamine contracts cerebral arteries via specific non-endothelial H1-receptors, and enhances perivascular adrenergic neurotransmission through specific presynaptic H1-receptors by a mechanism involving increases in noradrenaline release.