Female B6C3F1 mice were exposed to isobutyl nitrite (IBN) by inhalation at 0, 37.5, 75, or 150 ppm for 6 hr per day, 5 days per week for 15 weeks. The potential of this compound to induce immunotoxicity was assessed during the 3rd, 13th, 14th, and 15th week of exposure and after 2 weeks of recovery following the 15 weeks of exposure. Both systemic and lung immune functions were examined, including body and lymphoid organs weights, pulmonary macrophage function and host defense, expression of splenic lymphocyte cell-surface markers, natural killer cell function, mixed lymphocyte reaction, and induction of specific antibody to a T-cell-dependent antigen. There was a dose-related suppression of T-cell-dependent antibody-forming cell responses in the spleen following IBN exposure; however, other measures of T-cell and nonspecific immunity were not significantly affected. A dose-related increase of H202 production by alveolar macrophages was present after 12 but not after 68 exposures to IBN. In contrast, pulmonary host defense mechanisms against Klebsiella pneumoniae were unaffected. These results suggest that in the absence of changes in host resistance, IBN may have selective and partially reversible effects on the immune system.