Serotonin (5-hydroxytryptamine; 5-HT) modifies the responses to several vasoconstrictor stimuli prejunctionally and/or postjunctionally. The present study analyzed the effects of 5-HT on the pressor responses induced by norepinephrine (NE) or electrical sympathetic stimulation in pithed rats. Responses to intravenous (i.v.) NE (0.03-3 micrograms/kg) or electrical stimulation at increasing frequencies (0.1-3 Hz) were evaluated before and during continuous i.v. infusions of physiological saline (0.01 ml/min) or 5-HT (1-10 micrograms/kg x min). The effects of 5-HT on the tachycardic responses to NE and sympathetic stimulation were studied in parallel. The increases in diastolic blood pressure and heart rate produced by NE were not modified by 5-HT. In contrast, 5-HT significantly and dose-dependently inhibited the increases in diastolic blood pressure - but not those in heart rate - produced by stimulation of the appropriate spinal segments. These effects of 5-HT were more pronounced on the responses to lower frequencies of stimulation. It is suggested that 5-HT inhibits the electrically induced pressor responses by a prejunctional mechanism which would lead to a reduction of neurotransmitter release from the sympathetic nerves supplying the systemic vasculature. The selective stimulation of this inhibitory mechanism might represent a new approach for the development of novel antihypertensive agents.