The effect of depleting lung ascorbic acid (AH(sub 2)) and nonprotein sulfhydryls (NPSH) on the acute inhalation toxicity of nitrogen dioxide (NO(sub 2)), ozone (O(sub 3)), and phosgene (COCl(sub 2)) was investigated in guinea pigs. The increase in bronchoalveolar lavage (BAL) fluid protein (an indicator of alveolar-capillary damage leading to increased permeability) was measured 16 to 18 hr following a 4 hr exposure to the gas in animals deficient in (AH(sub 2)) or NPSH. Gas concentrations were chosen which produced low but significant increases in BAL protein. Lung (AH(sub 2)) was lowered to about 20% of control by feeding rabbit chow for 2 weeks. Lung NPSH was lowered to about 50% of control by injecting a mixture of buthionine S,R-sulfoximine (BSO) and diethylmaleate (DEM) (2.7 and 1.2 mmol/kg respectively). BSO/DEM did not affect the lung concentrations of (AH(sub 2)) or alpha-tocopherol. AH(sub 2) depletion caused a 6 fold and a 3 fold enhancement in the toxicity of 5 ppm and 10 ppm (NO(sub 2)), and a 6 fold enhancement in the toxicity of 0.5 ppm (O(sub 3)), but did not affect toxicity of 1.0 ppm (O(sub 3)). AH(sub 2) depletion did not affect phosgene toxicity (at 0.25 ppm and 0.5 ppm). (Copyright (c) 1989 by Hemisphere Publishing Corporation.)