Although a number of studies have demonstrated suppression of extrapulmonary immune responses following exposure to NO2, a ubiquitous ambient and indoor air pollutant, most of these studies have utilized extremely high concentrations of NO2 relative to the environment. The authors' intent was to assess effects of NO2 on extrapulmonary immune responses using an environmentally relevant exposure regimen. Rats were exposed for 1, 3, 13, 52, or 78 wk to air or a pattern of NO2 designed to mimic episodic pollution in urban areas at concentrations 2-5 times those commonly seen in such areas. Daily exposures consisted of 0.5 ppm for 16 h, a 6-h exposure spike during which the concentration rose to 1.5 ppm, remained there for 2 h, and then returned to 0.5 ppm, and a 2-h down time. There were no NO2-related changes in mitogen responses, although significant suppression of these responses in both air and NO2 groups was noted in spleen at 52 and 78 wk, and in PBL at 13, 52, and 78 wk, presumably due to aging. Suppression of NK-cell activity was noted after 3 wk of exposure but not after 1, 13, 52, or 78 wk of exposure. Age did not appear to affect NK-cell activity.