This study assessed the relationship between nitrogen dioxide inhalation and the development of pulmonary emphysema and investigated how the severity of preexisting emphysema brought about by protease (elastase) instillation into the lung may be augmented by a subchronic exposure to a relatively high concentration of nitrogen dioxide. Lungs of adult Fischer‐344 rats were evaluated for emphysematous changes after (1) a single intratracheal instillation of elastase (E), (2) a 25‐d exposure to 35 ppm nitrogen dioxide (NO2), and (3) elastase instillation followed by 25‐d exposure to 35 ppm NO2(E + NO2). Rats instilled with sterile normal saline and subsequently exposed to filtered air served as a control group (NS). Residual volumes (RV) of the NO2and NS groups were virtually identical, whereas the RV of the E and E + NO2lungs (2.3 and 2.3 ml, respectively) were significantly greater than those of the NS and NO2lungs (1.3 and 1.4 ml, respectively). Directionally similar changes in the excised lung volumes and total lung capacities were obtained with the E and E + NO2groups; NO2alone, however, did not alter these volumetric parameters. No differences in arterial blood gases and pH values, minute ventilation, or breathing frequencies were found among the experimental groups. The mean linear intercept values (MLI) obtained with the NS and NO2exposed lungs were essentially identical with average values of ∼62 μm. This morphometric parameter was substantially increased in the E‐ and E + NO2‐exposed lungs; no significant differences, however, were found between the MLI values obtained with the E and E + NO2lungs (∼95 and ∼97 μm, respectively). From these data, as well as histologic examinations of lung sections for evidence of emphysema, we conclude that (1) a subchronic, moderately high level of NO2exposure does not produce an irreversible emphysematous lesion in the rat model and (2) exposure of rats to 35 ppm for 25 d after elastase instillation into the lungs does not potentiate protease‐induced emphysema or bring about a progression in preexisting emphysema.