Vasoactive intestinal peptide, one of the putative neurotransmitters of non-adrenergic inhibitory nerves in human airways, is a potent relaxant of human airways in vitro. Previous in vivo studies of infused vasoactive intestinal peptide in asthmatic subjects have shown only a small bronchodilator effect, which may have been secondary to the cardiovascular effects of the peptide. The effect on airway function of infused vasoactive intestinal peptide was studied in normal subjects, who readily develop bronchodilation in response to a beta agonist. Separate experiments were designed to assess whether there is any synergy between this peptide and the beta agonist isoprenaline. Incremental doses of 1, 3, and 6 pmol/kg/min of vasoactive intestinal peptide were infused for 15 minutes. At 6 pmol/kg/min it caused a mean fall in systolic blood pressure from 108 to 88 mm Hg and a rise in heart rate from 71 to 95 beats/min. There was no significant change in specific airways conductance (sGaw) at any dose of vasoactive intestinal peptide. No significant changes were found with placebo. Isoprenaline (400 microgram) given by inhalation at the end of the infusion produced a mean increase in sGaw of 50%. Infused peptide caused no significant change in the cumulative dose-response curve for inhaled isoprenaline. The lack of effect of vasoactive intestinal peptide on airway responses in vivo may be due to rapid enzymatic breakdown of the peptide or to the fact that dosage has to be limited by the cardiovascular effects.