A factorial design study was performed to examine the acute effects of inhaled acid particles alone and in mixtures with ozone to test the hypothesis that acid particles and ozone would act synergistically. Sprague-Dawley rats were exposed nose-only for a single 4-h period to all 9 possible combinations of purified air and 2 concentrations each of O(3) (0.3 and 0.6 ppm) and submicrometer (0.3 μm mass median diameter [MMD]) sulfuric acid aerosols H(2)SO(4) (0.5 and 1.0 mg/m(3)). Respiratory-tract injury and impairment of alveolar macrophage functions were evaluated. Two-way analyses of variance were used to test for significance of main effects and statistical interactions, and Tukey multiple comparison tests were used to test the significance of differences between group mean values. Addition of H(2)SO(4) to O(3)-containing atmospheres resulted in significant H(2)SO(4) concentration-dependent reductions in O(3)-induced inflammatory responses, and H(2)SO(4), alone and in combination with O(3), depressed some functions of innate immunity. DNA synthesis in nasal, tracheal, and lung tissue following pollutant exposure, which is an index of injury or killing of epithelial cells, was significantly increased by O(3) but not by H(2)SO(4) when administered alone, compared to purified air. When administered with O(3), H(2)SO(4) did not reduce the effects of O(3) on DNA synthesis in the trachea or the lung, but did reduce the DNA synthesis response to O(3) in the nose. No significant changes in antibody-directed Fc receptor (FcR) binding of sheep red blood cells by alveolar macrophages were observed, but macrophage phagocytic activity was significantly reduced by the pollutant exposures. In summary, the results of this study indicate significant interactions between O(3) and H(2)SO(4) in concurrent exposures; however, the findings do not support the hypothesis that O(3) and H(2)SO(4) act synergistically in rats after single 4-h exposures.