1 Three methods have been used in an attempt to study the interactions of tryptamine with central 5-hydroxytryptamine (5-HT) systems. 2 In grups of mice pretreated with tranylcypromine, tryptamine reduced the number of mice showing head twitches following the 5-HT precursor, 5-hydroxytryptophan. This effect was not seen in mice pretreated with saline and tryptamine itself did not induce head twitches in either group. 3 The swallowing reflex induced by 5-hydroxytryptophan in rats anaesthetized with urethane was substantially reduced by tryptamine injected into the internal carotid artery. This effect was seen in rats pretreated with saline or tranylcypromine, in the latter case the effects being more profound and longer lasting. In addition, swallowing evoked by the 5-HT uptake blocker, fluoxetine, and the 5-HT releaser, p-chloroamphetamine, was also reduced by tryptamine. 4 5-HT or noradrenaline injected intravenously into 5 day-old chicks caused a dose-dependent behavioural depression resembling sleep. Tryptamine at high doses caused behavioural alerting effects. Tryptamine at low doses had no overt effects but enhanced depression induced by 5-HT. At behaviourally excitatory doses tryptamine reduced the duration of the 5-HT depression. Noradrenaline-induced depression was not affected by high or low doses of tryptamine. 5 The results show that tryptamine can have complex actions on 5-HT systems depending on the parameter studied and support the notion that tryptamine may be a controlling factor in 5-HT-mediated transmission.