Hyperpnoea with dry air could lead to a reduction in depth and hyperosmolarity of the periciliary fluid layer (PFL) as a consequence of evaporative water loss. We investigated whether mucociliary clearance (MCC) is likely to be affected by dry air hyperpnoea, which also results in airway narrowing in asthmatics. MCC was measured by radioaerosol technique, for about 1 h, in 10 asthmatic and 8 healthy subjects on 3 separate days: 1) nasal resting breathing with ambient air; 2) isocapnic hyperventilation (ISH) with dry air; and 3) ISH with warm humid air. Analysis of the initial and post-intervention lung radioactivity for the whole right lung and for defined regions of interest showed that, compared to ISH with warm humid air and nasal resting breathing, MCC was reduced during and increased post-ISH with dry air in the whole right lung of both groups. The mean reduction in clearance (+/- 95% confidence interval (95% CI)) was -9.3% (-3.1 to -15.6%) and -3.6% (-2.0 to -9.1%), and the mean increase (+/- 95% CI) was 19.2% (11.8 to 26.6%) and 14.8% (7.1 to 22.5%), compared to warm humid air, in asthmatic and healthy subjects, respectively. However, regional analysis showed that the changes were present in all lung regions of the asthmatics, whilst only in the central region of the healthy subjects. The duration of the increased clearance rates post-ISH was also different in both groups. The changes in mucociliary clearance during and after isocapnic hyperventilation with dry air was probably related to the water content of the inspired air, causing transient changes in the periciliary fluid layer.