Reboxetine is a novel antidepressant with a potent noradrenaline uptake-inhibiting property, but with little anity for neurotransmitter receptors. Desipramine is a classical tricyclic antidepressant which, apart from inhibiting noradrenaline uptake, also has anity for muscarinic cholinoceptors and a 1 -adrenoceptors, which can result in unwanted side eects. Single doses of reboxetine (1, 2 and 4 mg) and desipramine (25, 50 and 100 mg), were compared with placebo in 37 healthy volunteers, on several autonomic functions. Reboxetine antagonised tyramineevoked mydriasis, indicating noradrenaline-uptake blockade in the iris. The antidepressant increased blood pressure, heart rate, and resting pupil diameter and shortened the recovery time of the light reΒ―ex response consistent with a sympathomimetic eect resulting from noradrenaline-uptake blockade in peripheral tissues. Both antidepressants reduced salivation and light reΒ―ex amplitude, but failed to antagonise pilocarpine-evoked miosis, a response mediated by muscarinic cholinoceptors. Therefore, the eects on salivation and light reΒ―ex amplitude are unlikely to be due to muscarinic receptor blockade, but may rather reΒ―ect enhancement of noradrenergic inhibition of central parasympathetic nuclei as a result of noradrenaline-uptake blockade. Both antidepressants failed to antagonise phenylephrine-evoked sweating and methoxamine-evoked mydriasis, responses mediated by a 1 -adrenoceptors, consistent with their low anity for these receptors.