1. Intraperitoneal (i.p.) injection of 200-600 μmol/kg of cytidine-5′-diphosphocholine (CDP-choline) increased plasma adrenaline and noradrenaline concentrations dose- and time-dependently. 2. CDP-choline treatment caused several-fold increases in plasma concentrations of CDP-choline and its metabolites phosphocholine, choline, cytidine monophosphate (CMP) and cytidine. 3. Equivalent doses (200-600 μmol/kg; i.p.) of phosphocholine or choline, but not CMP or cytidine, increased plasma adrenaline and noradrenaline dose-dependently. 4. CDP-choline, phosphocholine and choline (600 μmol/kg; i.p.) augmented the increases in plasma adrenaline and noradrenaline in response to graded haemorrhage. 5. The increases in plasma adrenaline and noradrenaline induced by i.p. 600 μmol/kg of CDP-choline, phosphocholine or choline were abolished by pre-treatment with hexamethonium (15 mg/kg; i.p.), but not atropine (2 mg/kg; i.p.). 6. At 320-32 000 μm concentrations, choline, but not CDP-choline or phosphocholine, evoked catecholamine secretion from perfused adrenal gland. Choline (3200 μm)-induced catecholamine secretion was attenuated by the presence of 1 μm of hexamethonium or mecamylamine, but not atropine, in the perfusion medium. 7. Intracerebroventricular (i.c.v.) injection of choline (0.5-1.5 μmol) also increased plasma adrenaline and noradrenaline dose- and time-dependently. Pre-treatment with mecamylamine (50 μg; i.c.v.) or hexamethonium (15 mg/kg; i.p.), but not atropine (10 μg; i.c.v.), prevented i.c.v. choline (1.5 μmol)-induced elevations in plasma adrenaline and noradrenaline. 8. It is concluded that i.p. administration of CDP-choline or its cholinergic metabolites phosphocholine and choline increases plasma adrenaline and noradrenaline concentrations by enhancing nicotinic cholinergic neurotransmission in the sympatho-adrenal system. Central choline also activates the sympatho-adrenal system by increasing central nicotinic cholinergic neurotransmission. © 2008 The Authors.