Inhaled cigarette smoke releases a variety of oxidizing agents. Ascorbic acid is recognized as an important biological antioxidant. To better characterize the antioxidant protective role of ascorbic acid, a comparison of ascorbic acid concentrations in plasma, leukocytes, bronchoalveolar lavage fluid and alveolar macrophages from a homogeneous group of healthy male smokers (n = 10) and nonsmokers (n = 14) was investigated. The resulting ascorbic acid contents were (means +/- SD) 91 +/- 25 (n = 10) and 87 +/- 25 (n = 14) mumol/L in plasma, 2.09 +/- 0.62 (n = 7) and 2.12 +/- 0.77 (n = 11) mumol/10(9) cells in mononuclear leukocytes, 3.2 +/- 2.2 (n = 10) and 1.7 +/- 1.5 (n = 13) mumol/L in bronchoalveolar lavage fluid and 3.4 +/- 2.3 (n = 8) and 1.6 +/- 1.3 (n = 6) mumol/10(9) cells in alveolar macrophages from smokers and nonsmokers, respectively. Mean daily dietary vitamin C intake was 116 +/- 68 and 107 +/- 59 mg/d for smokers and nonsmokers, respectively. The ascorbic acid contents of bronchoalveolar lavage [3.9 +/- 1.9 mumol/L (n = 8)] and alveolar macrophages [4.1 +/- 2.1 mumol/10(9) cells (n = 6)] of smokers consuming 15 to 20 cigarettes/d were significantly higher (P less than 0.05) than those of nonsmokers. The increased content of ascorbic acid in bronchoalveolar lavage and in alveolar macrophages of smokers compared with nonsmokers may reflect a defensive mechanism against free radical species derived from cigarette smoke.