Peptide histidine valine (PHV) is a 42 amino acid polypeptide closely related to the neuropeptides VIP, PHI and PHM. We have performed a placebo-controlled, double-blind study to assess the hypothesis that the cardiovascular response to PHV infusion may be mediated via the sympathetic nervous system. Four subjects received atenolol or matched placebo 90 min prior to a controlled incremental infusion of PHV, with monitoring of heart rate, blood pressure and skin temperature. Following placebo all subjects showed a dose-related increase in heart rate and skin temperature with no effect on blood pressure during PHV infusion. beta-Blockade had no effect on skin temperature response. Pre-treatment with atenolol reduced the resting blood pressure and the maximum heart rate achieved, but did not affect the percentage increase in heart rate during PHV infusion. This suggests that the action of PHV does not involve beta-receptors. The lack of effect of PHV infusion on blood pressure, despite tachycardia and marked cutaneous vasodilatation, implies that PHV has a different effect on the resistance vessels from that of other peptides such as VIP.