We have examined the influence of total intrapulmonary deposition and its pattern on the bronchial response to aerosolized methacholine and atropine in 10 normal and 12 asthmatic subjects. On Day 1 we performed a dose-response challenge to methacholine and defined responsiveness as the provocative dose (PD35) needed to cause a 35% decrease in specific airway conductance (SGaw). On Day 2 we repeated methacholine challenge after premedication with aerosolized atropine, and we defined the response to atropine as dose ratio-1 (DR-1) where DR = PD35 after atropine/PD35 without atropine. On Day 3 we imaged intrapulmonary aerosol deposition by mixing 99mtechnetium with methacholine aerosol and scanning the thorax with a gamma camera during the development of bronchoconstriction. Total pulmonary aerosol deposition varied considerably between individuals (1.2 to 23.6% of nebulized dose) but there was no difference between normal and asthmatic subjects, and no correlation between deposition and baseline SGaw or PD35; there was a significant positive correlation between deposition and DR-1. Deposition of aerosol in central lung zones was inversely related to SGaw and correlated positively with DR-1; there was no significant relationship with PD35. Total intrapulmonary aerosol deposition and its pattern partially determine bronchial responsiveness to atropine, but we have not demonstrated any significant effect on responsiveness to methacholine.