The effect of inhaled histamine on human tracheal mucus velocity (TMV) and bronchial mucociliary clearance (CB) was investigated in six healthy subjects using radioaerosol techniques in a randomized double-blind crossover study. Subjects inhaled repeated doses of either phosphate-buffered saline (PBS) or histamine, immediately after the inhalation of a radioaerosol and during the subsequent 2.5-h clearance measurements. Histamine was administered in concentrations previously demonstrated to induce a 20% fall in FEV1 at intervals permitting 90% recovery (mean recovery time = 25 min). Both TMV and CB were significantly increased by inhaled histamine (p less than 0.001). Average TMV throughout the 2.5-h studies increased from 4.9 +/- 1.3 to 8.4 +/- 1.6 mm/min. The increase in TMV above control values became apparent from 5 to 20 min after the first histamine administration. The percentage of aerosol clearance in 60 min increased 33%. The enhancement of CB became statistically significant at 21 min and persisted throughout the 2.5-h measurements (p less than 0.05). The increase in CB could not be attributed to differences in aerosol deposition because measurements of aerosol penetration were not significantly different between PBS and histamine studies. These data indicate that the bronchoconstriction caused by histamine is accompanied by an increase in tracheal and bronchial mucus transport. Release of histamine, as part of an inflammatory response, may alter mucociliary clearance in humans.