Vasoactive intestinal polypeptide (VIP) is a neuropeptide present in the nerve fibers of normal lungs, where it acts to relax bronchial smooth muscle. To determine its presence or absence in the lungs of patients with asthma, we examined lung tissue obtained at autopsy or lobectomy from five patients with asthma and nine without asthma. The avidin-biotin-peroxidase complex technique was used to stain tissue for immunoreactivity to VIP. At least 80 tissue sections from each patient were examined microscopically; the airway diameter ranged from 100 microns to 1.2 cm. Immunoreactive VIP was seen within nerves in more than 92 percent of the sections from the lungs of patients without asthma. No VIP was seen in any of 468 sections we could evaluate that were obtained from the lungs of patients with asthma. As a control for the nonspecific destruction of neuropeptides, immunostaining for substance P was also carried out. Abundant amounts of this neuropeptide were seen within nerves in tissue from the lungs of all patients. We conclude that in patients with asthma there is a loss of VIP from the pulmonary nerve fibers that may diminish neurogenically mediated bronchodilation. Whether this loss is a cause or a result of asthma is unclear.