Inhalation of Tobacco smoke (TS) by rats for 1 h caused significant depletions in the free glutathione (GSH) of homogenate supernatants of whole lung (13.9-8.8 mumol/g protein), lavage cells (2.7-1.7 nmol/10(6) cells) and lavage fluid (1.3-0.4 microM). In each case the depletions were nonrecoverable by dithiothreitol (DTT) suggesting conjugation between GSH and TS-borne electrophiles. Corresponding lung cysteine (CySH) components were unaffected by TS inhalation. In contrast, TS inhalation had no effect on the blood plasma GSH redox balance at various points around the circulation, but was shown to affect those of CySH, causing significant reductions in total CySH in plasma samples obtained both pre- and postpulmonarily. Similarly, the redox status of GSH in homogenate supernatants of whole liver was unaffected by TS inhalation, but there were significant increases in hepatic free CySH. These results indicate that acute TS inhalation increases the oxidant burden on the lungs causing a transient depletion of GSH in a variety of pools. Concurrently, the lungs may possess regulatory mechanism(s) which respond immediately by the uptake of CySH equivalents present in plasma disulfides.