We studied the effects of ozone (O3) and histamine on the lung periphery. A fiber-optic bronchoscope was wedged in a segmental airway of anesthetized male mongrel dogs. Measurements of collateral resistance (Rcoll) were used to monitor responses to O3 and to histamine. Both agents were delivered locally through the bronchoscope. During a 30-min exposure to 0.1 ppm O3, Rcoll increased 31.5 +/- 5.1% within 2 min and then gradually decreased toward control levels in spite of continued exposure to O3. Within 15 min after the exposure ceased, Rcoll had returned to base line. Subsequent exposure to 0.1 ppm O3 did not increase Rcoll. During a 30-min exposure to 1.5 X 10(-6) mg/min histamine aerosol, Rcoll increased 21.5 +/- 5.0% within 2 min and persisted at an elevated level throughout the exposure. Subsequent exposures to histamine produced similar increases in Rcoll. Bilateral cervical vagotomy or pretreatment with atropine aerosol (0.1 mg) prevented responses to O3 but did not prevent responses to histamine. These results indicate that responses to O3, unlike responses to histamine in the lung periphery, are characterized by the rapid development of adaptation and tolerance and are mediated through the vagus nerves.