The influence of sympathetic and parasympathetic controls on regional particle deposition and mucociliary clearance rates was studied in the donkey in vivo. The deposition and clearance characteristics for gamma-tagged monodisperse ferric oxide microspheres were determined for inhalation tests after atropine and methacholine injections and were compared with the characteristics determined for control tests with the same animals and aerosols. Additional tests were performed in which methacholine was injected immediately after the test aerosol inhalation and 2 1/2 h before the particle inhalation. Particle deposition is shifted distally by atropine. Methacholine produces a proximal shift initially and a distal shift 2 1/2 h later. Atropine slows mucociliary transport. Methacholine produces an acceleration in bronchial clearance initially but causes a reduced rate of clearance 2 1/2 h later. Atropine slows mucociliary transport. Methacholine produces an acceleration in bronchial clearance initially but causes a reduced rate of clearance 2 1/2 h later. It also produces an initial surge in tracheal transport, which frequently leads to tracheal mucus refluxing and thereby an increase in average tracheal residence time. The drugs were used to modify the normal deposition and clearance characteristics of a particular animal so that they resembled the normal characteristics of a different animal, suggesting that much of the large intersubject variability may be attributable to different levels of autonomic tone.