Bronchial reactivity to methacholine (MCH) under normoxic and hyperoxic conditions was studied in a double-blind controlled study in 10 normal subjects and nine asthmatic patients. The normal volunteers were challenged while breathing dry, 21% and 100% O2, and the maximal percent falls in forced expired volume in is (FEV1) following inhalation of the highest concentration of MCH (64 mg/ml) were 8 +/- 5% and 9 +/- 8%, respectively; P = NS. The asthmatic patients had their MCH challenge breathing the same gas composition and the provocative concentrations that caused a 20% fall in FEV1 (PC20) were 0.18 mg/ml (range 0.06-5.73) and 0.25 mg/ml (range 0.07-8.49), respectively, which were statistically not significantly different. We conclude that in humans, 100% O2 does not affect bronchial reactivity to MCH.