Effects of increased ambient pressure on mucociliary clearance have been poorly investigated. The effects of increasing pressures on ciliary beat frequency (CBF) of guinea-pig tracheal rings were studied in vitro. Increased pressures of 25 and 100 kPa induced a significant and equivalent enhancement of CBF from 30 min after the pressure increase. The increase in CBF observed after a pressure increase of 50 kPa (inspiratory oxygen fraction = 21%), was significantly greater than that observed with an equivalent oxygen tension at atmospheric pressure, i.e. with a gas mixture containing 30% oxygen. Addition of N(G)-nitro-L-arginine methylester (L-NAME) inhibited the enhancement in CBF observed after the 25 kPa pressure increase. Addition of L-arginine reversed the effect of L-NAME. These results demonstrate that a pressure increase applied to tracheal rings, in vitro, induces an enhancement of ciliary beat frequency and that generation of nitric oxide may be involved in this ciliary stimulation.