The (R)-enantiomer of racemic albuterol produces bronchodilation, whereas the (S)-enantiomer may increase airway reactivity. After oral or intravenous administration of racemic albuterol, the (R)- enantiomer is metabolized several times faster than the (S)-enantiomer; however, enantiomer disposition after inhaling racemic albuterol with a metered-dose inhaler (MDI) is not known. Accordingly, 10 healthy subjects inhaled racemic albuterol with a MDI alone and with a MDI and holding chamber. We measured plasma levels of unchanged (R)- and (S)-albuterol before and up to 4 h after inhalation of racemic albuterol, and determined the unchanged R/S ratio in urine before and at 0.5, 4, 8, and 24 h later. The disposition of albuterol's enantiomers with a MDI and holding chamber was similar to that with a MDI alone. The area under the curve (AUC) of the plasma levels over time was significantly lower for the (S)- than for the (R)-enantiomer-395.5 +/- 141.0 (SE) versus 882.7 +/- 126.4 ng. ml(-)(1). min (p < 0.05)-indicating preferential retention of (S)-albuterol in the lung. The R/S ratio in urine at 0. 5 h after albuterol was > 1, reflecting the higher plasma level of the (R)-enantiomer. In conclusion, preferential retention of the (S)- compared with the (R)-enantiomer in the lung could lead to accumulation of the (S)-enantiomer after long-term use of racemic albuterol.