BACKGROUND Repeated, short-term exposures to ozone (O3) lead to attenuation of the acute lung function and airway inflammatory responses seen after a single exposure in healthy subjects, but it is unclear whether these acute responses also attenuate in subjects with asthma. OBJECTIVE To address this question by exposing 14 subjects with asthma to 0.2 ppm O3 for either 4 hours on a single day or 4 hours on 4 consecutive days (multiday [MD]). At least 3 weeks later, subjects underwent the alternate exposure. METHODS Spirometry was performed immediately pre- and postexposure and bronchoalveolar lavage (BAL) was obtained 18 hours after each exposure. RESULTS The decrease in FEV1 was greatest across Day 2 of the MD (MD2) exposure and then gradually declined on successive days of the MD exposure (mean +/- SD decrease in FEV1 of 25.4 +/- 18.0% across MD2 compared with 4.2 +/- 6.5% across MD4). Respiratory symptoms followed a similar pattern to that of FEV1. Although the concentration of neutrophils in BAL after the MD4 exposure was not significantly different from that after the single-day exposure (1.7 +/- 1.3 x 10(4) cells/ml vs. 1.2 +/- 0.8 x 10(4) cells/ml, p = 0.20), the concentration of alveolar macrophages did significantly increase in BAL after the MD exposure (19.9 +/- 9.7 x 10(4) cells/ml after MD4 vs. 12.1 +/- 6.4 x 10(4) cells/ml after the single day). CONCLUSIONS Alveolar macrophages are recruited to the airways of subjects with asthma with repeated short-term exposures to O3, suggesting a possible role for these cells in the chronic response to oxidant-induced injury.