The effect of prior ozone (03) exposure on airway hyperresponsiveness and inflammation induced by trimellitic anhydride (IMA) has been investigated in TMA-sensitized guinea pigs. Airway responsiveness was measured as the concentration of acetylcholine needed to increase baseline lung resistance (RL) by 300% (PC300). Ozone (3 ppm for 3 h) caused an increase in -log PC300 at 1 h after exposure, with return of-log PC300 to control levels at 8 h. Ozone also increased baseline RL at 8 h. TMA challenge increase -log PC300 in TMA-sensitized guinea pigs at8h after challenge from 3.85 ± 0.09 to 4.11 ± 0.09. Ozone exposure prior to TMA challenge prevented the induction of airway hyperresponsiveness with a mean -log PC300 of 3.51 ± 0.20, which was not different from that of control TMA-sensitized group. Baseline RL was significantly higher in ozone-pretreated animals after TMA challenge when compared to those of either control or challenged with TMA alone. Ozone had no effect on TMA challenge-induced BAL eosinophilia and neutrophilia. We conclude that a single exposure to ozone inhibits the increase in airway responsiveness but increases the bronchoconstrictor response induced by TMA in TMA-sensitized guinea pigs; however, the inflammatory airway response to TMA is unchanged by preexposure to ozone.