Amounts of salbutamol delivered from chlorofluorocarbon (CFC)-free metered dose inhalers (MDIs) (Airomir; 3M, St. Paul, MN) in particle sizes appropriate for inhalational treatment with five common holding chambers (NES [or Nebuchamber] spacer [Astra Draco AB, Lund, Sweden], AeroChamber [Trudell Medical, London, Ontario, Canada], OptiChamber [Health-scan Products, Cedar Grove, NJ], Vent170 spacer [Nordac Design, Waterloo, Ontario, Canada], and E-Z Spacer [WE Pharmaceuticals, Ramona, CA]) when used under simulated pediatric tidal breathing conditions were determined. Five devices of each type were tested with Airomir hydrofluoroalkane (HFA) inhalers (100 micrograms of salbutamol). Each device was connected to face replicas representative of 7-month-old (infant) and 2-year-old (toddler) children, and aerosol was also inhaled into an Andersen cascade impactor (Graseby Andersen, Smyrna, GA) using a valve system and simulated tidal breathing patterns representative of children of these ages. Amounts of drug inhaled in fine particles with the HFA formulation are significantly less (up to 46% less) with the E-Z Spacer (P < 0.01) compared with amounts inhaled in previous studies with the CFC formulation but are nearly the same with other holding chamber types (e.g., differing by < 6% for the AeroChamber). With the HFA formulation, the metal NES spacer delivered significantly more salbutamol in fine particles (P < 0.01) than any of the other holding chambers. Amounts of salbutamol inhaled in fine particles during pediatric tidal breathing from valved holding chambers with Airomir varies considerably between holding chamber types.