In the present study we investigated the effects of microinjection into the commissural nucleus tractus solitarius (NTS) of unanesthetized rats of 2-methylserotonin (2-methyl-5-HT), a 5-HT3 receptor agonist, on the cardiac component of the baro- and chemoreflexes. The study was performed in conscious freely moving rats in order to avoid the possible effects of anesthetics on the cardiovascular responses to microinjection of neuroactive substances into the NTS. The baroreflex (phenylephrine, 0.5-2.0 micrograms/kg, i.v.) and the chemoreflex (potassium cyanide, 40 micrograms/rat, i.v) were activated in different groups of rats before and after bilateral microinjection of 2-methyl-5-HT into the NTS. Microinjections of 2-methyl-5-HT (5 nmol/50 nl) into the NTS produced a significant increase in basal mean arterial pressure (101 +/- 3 versus 125 +/- 8 mmHg), no changes in basal HR and a significant reduction in the reflex bradycardia triggered by baroreflex activation at 3 (-28 +/- 7 bpm), 10 (-35 +/- 4 bpm) and 20 min (-34 +/- 5 bpm) in comparison with the control value (-68 +/- 9 bpm). A similar reduction in the bradycardic response to chemoreflex activation was observed at 3 (-94 +/- 35 bpm), 10 (-98 +/- 38 bpm) and 20 min (-110 +/- 29 bpm) after 2-methyl-5-HT in comparison with the control value (-178 +/- 19 bpm). The effect of 2-methyl-5-HT on the basal mean arterial pressure and on the bradycardia evoked by stimulation of the baro- and chemoreflexes was blocked by pretreatment with granisetron bilaterally microinjected (500 pmol/50 nl) into the NTS. The data show that the stimulation of 5-HT3 receptors in the NTS of unanesthetized rats elicits a significant increase in basal mean arterial pressure and decreases the bradycardic response to baro- or chemoreflex activation.