Monodisperse aerosols were used to determine airway dimensions as a function of volumetric lung depth in vivo. Two different techniques were compared in anesthetized mechanically ventilated dogs (mean body wt. +/- SD, 13.6 +/- 0.9 kg). Monodisperse di-(2-ethyl-hexyl) sebacate particles (mean aerodynamic diameter +/- SD, 0.89 +/- 0.097 mum) were inhaled as bolus (half-width 8 ml) at 10-85% of the normalized (50% functional residual capacity, FRC) inspired volume (Bolus Technique). Alternatively, the total inspired volume contained the test aerosol, formally representing inspiration of a train of aerosol boluses of infinitesimal small volume (Single-Breath Technique). The particle concentration was continuously recorded ai the airway opening by a miniaturized in-line aerosol photometer incorporating a 2 mW laser diode (lambda = 820 nm) and a photodiode. The airway diameters determined at a given volumetric lung depth were related to the animal's total lung capacity (TLC) to account for lung volume differences between dogs. The in-vivo aerosol-derived airway diameters of dog lungs revealed close correspondence with morphometric estimates from excised lungs. No systematic differences were found between the two aerosol techniques. The coefficient of variation for repeated measurements was < 3% for the single-breath technique and about 10% for the bolus technique. The estimation of aerosol-derived airway diameters by the single-breath method displays several advantages over the bolus technique: i) less time-consuming, ii) better spatial resolution, and iii) higher reproducibility.