Using the wedged bronchoscope technique to measure collateral resistance (Rcs), we evaluated the effect of succinylcholine (SCh) on the response to acetylcholine (ACh) and methacholine (MCh) in the lung periphery in six mongrel dogs. Dogs were anesthetized, intubated, and mechanically ventilated. After a stable baseline Rcs was obtained, responses to intravenous ACh (25-200 micrograms), intravenous MCh (3-30 micrograms), and aerosolized ACh (30-100 micrograms/ml for 15 s) were measured. We compared the Rcs responses with 1) ACh alone, 2) ACh 2 min after SCh (0.5 mg/kg), 3) ACh 2 min after SCh and during hexamethonium infusion (5 mg/kg + 10 mg.kg-1.h-1), 4) MCh 2 min after SCh, and 5) ACh aerosol 2 min after SCh. SCh did not significantly alter baseline airway tone. SCh increased the Rcs response to ACh by 48 +/- 17% (SE) (P less than 0.01). SCh in the presence of hexamethonium increased the Rcs response by 10 +/- 3% (P less than 0.05), while hexamethonium itself increased the response to ACh by 69 +/- 27%. Because SCh did not increase the Rcs response to intravenous MCh or to aerosolized ACh, SCh probably enhances airway reactivity to intravenous ACh by competing for pseudocholinesterase in plasma. We conclude that the level of muscle relaxant must be taken into account in interpreting studies of airway reactivity when intravenous ACh is employed.