In the present study, we investigated (1) whether airway responsiveness to inhaled histamine‐aerosol could be induced during 7‐d exposure of guinea pigs to 4 ppm NO2and, if so, (2) whether thromboxane A2may be involved in such increase. Female Hartley guinea pigs were divided into 6 groups (n ‐ 15/group). Three groups were exposed to filtered air and the other 3 groups were exposed to NO2for 1, 3, or 7 d (24 h/d). Baseline specific airway resistance (SRaw0) did not change significantly after exposure to 4 ppm NO2or air. Airway responsiveness was determined 1 wk before the beginning of exposure and on the day of termination of the exposure. Prior to exposure to NO2the EC200His, the concentrations of inhaled histamine necessary to double SRawNaCl(SRaw after inhalation of 0.9% NaCI), were 1.07 ± 0.20, 1.30 ± 0.20, and 1.01 ± 0.18 mM for the 3 groups later given NO2for 1, 3, and 7 d, respectively. Following exposure to NO2for 1, 3, or 7 d, EC200His values were 1.42 ± 0.25, 0.66 ± 0.10 (p < .05), and 1.05 ± 0.22 mM, respectively. These results show that 7‐d exposure to 4 ppm NO2induced a significant increase in airway responsiveness on d 3. Exposure to air had no significant effect on the airway responsiveness. This transient hyperresponsiveness was inhibited by a specific inhibitor of thromboxane synthetase, OKY 046. These results indicated that (1) a lower concentration (4 ppm) of NO2than that previously reported can induce transient hyperresponsiveness in guinea pigs during appropriate long‐term exposure, and (2) thromboxane A2may play an important role in this transient airway hyperresponsiveness.