The influence of the parasympathetic nervous system on the cardiovascular response to a synthetic atrial peptide (atriopeptin III) was examined in conscious normotensive rats utilizing the technique of radiolabelled microspheres. Atriopeptin III was infused intravenously for 30 min at a rate of 1 microgram/min in rats pretreated with a bolus intravenous injection of atropine, 150 micrograms (n = 8), or of its vehicle (n = 8). Additional animals (n = 9) received the vehicle of both atropine and atriopeptin III. The atrial peptide decreased mean blood pressure to similar extent in rats pretreated with atropine (from 124 +/- 4.5 to 108 +/- 5.3 mmHg, mean +/- SEM, p less than 0.05) and in the controls (from 123 +/- 3.8 to 105 +/- 3.8 mmHg, p less than 0.05). Heart rate rose significantly after administration of atropine. After the 30 minute infusion, cardiac index was significantly lower (p less than 0.05) in both groups infused with atriopeptin III (23.4 +/- 2.3 after atropine pretreatment and 25.1 +/- 2.2 ml/min X 100 g without atropine) than in the group of rats given only the vehicle of both atropine and atriopeptin III (32.4 +/- 2.8 ml/min X 100 g). There was no significant difference in regional blood flow distribution within the three groups of rats. These data therefore indicate that in conscious rats atriopeptin III reduces blood pressure and cardiac output without concomitantly modifying regional blood flow distribution. They also suggest that the parasympathetic nervous system does not contribute to the hemodynamic response to atriopeptin III.