1 A study was made of the effects of 5-hydroxytryptamine (5-HT) on presser response induced in vivo by electrical stimulation of the sympathetic outflow from the spinal cord of pithed rats. All animals had been pretreated with atropine. Intravenous infusion of 5-hydroxytryptamine at doses of 10 and 20 mu g kg(-1) min(-1) reduced the presser effects obtained by electrical stimulation at intervals of 10 min over the 1 h of infusion. 2 This inhibitory action of 5-HT was depressed by cyproheptadine and methiothepin but was not modified by ketanserin or MDL-72222. By contrast, the inhibitory action of 5-HT was lost in pithed rats that had been pretreated with exogenous noradrenaline. 3 The 5-HT1 receptor agonist 5-carboxamidotryptamine (5-CT) caused an inhibition of the presser response, whereas the 5-HT3 receptor agonist, 1-phenylbiguanide, produced a variable but significant increase in the presser response. The 5-HT2 receptor agonist, m-CPP, did not modify the presser sympathetic response. 4 Our results suggest that 5-hydroxytryptamine interferes with sympathetic neurotransmission by inhibiting presser effects as a result of stimulation of the complete sympathetic outflow, and that this inhibition is mainly through a presynaptic 5-HT1 mechanism.