||The low tidal volume and flow in preschool children may reduce the efficiency of aerosol delivery from a pressurized metered-dose inhaler (pMDI) through a traditional holding chamber. A prototype small-volume steel holding chamber with two one-way valves was devised to prolong aerosol availability in the chamber and to ensure unidirectional airflow. Dead space between the valves was minimized to less than 2 ml. The dose-delivery and rate of passive disappearance of a budesonide pMDI aerosol were compared between this prototype and the large-volume, single-valved plastic Nebuhaler, in 164 asthmatic children less than 8 yrs of age. In vitro, the half life of aerosol disappearance in the steel prototype and the plastic Nebuhaler was > 30 s and 9 s, respectively. In vivo, the prototype delivered an age-independent mean dose of 38% of the nominal dose, and the Nebuhaler delivered an age-dependent mean dose, ranging from 42% of the nominal dose in children > or = 4 yrs to 19% of the nominal dose in infants. We conclude that the use of plastic for holding chambers may influence dose-delivery, and single-valve control may cause age-dependent dose-delivery. Reproducible age-independent drug-delivery may be achieved by pMDI aerosol inhaled through a small-volume metal holding chamber with separate inlet and outlet valves and minimized dead space. This holding chamber would improve the possibilities of aerosol therapy for young children.