The influence of 5-hydroxytryptamine (5-HT) on the activity of the respiratory and vasomotor centers was studied by injecting 5-HT into the lateral and fourth ventricles of lightly anaesthetized cats. 50 and 500 mu g of 5-HT injected into the lateral ventricle induced a shortlasting increase in frequency and/or tidal volume followed by a prolonged and dose-dependent reduction of frequency, tidal volume and minute volume, concurrent with an increase in end expiratory CO2. The CO2 responsiveness of the respiratory center was depressed and the blood pressure levels were also lowered. All these effects were markedly enhanced by monoamine oxidase inhibition with i.v. tranylcypromine injected 75 min prior to 5-HT. 50 mu g of 5-HT injected into the fourth ventricle induced a depression of respiration similar to that observed in the lateral ventricle studies, with the exception that the early stimulation was abolished.