The protective effect of N-acetylcysteine on the toxicity of tobacco smoke condensates was investigated using different cellular in vitro systems. Cigarette smoke condensates, and the non-volatile and semi-volatile fractions separated from the condensate were used. All three smoke condensate fractions were toxic to isolated rat hepatocytes and lung cells and caused a loss of cell membrane integrity. A rapid depletion of cellular reduced glutathione (GSH) preceded the toxicity. The loss of GSH was due to conjugation of reactive compounds in the condensate fractions and not to oxidation since no increase in oxidized glutathione (GSSG) could be observed. N-acetylcysteine at a concentration of 1 mM protected both from the GSH loss and cell toxicity caused by the condensate fractions. The effect of the tobacco smoke condensate on the colony forming efficiency (CFE) of cultured human bronchial cells was also investigated. Already at concentrations of 50 micrograms/ml the survival decreased to 40% of control and at 100 micrograms/ml almost no cells formed colonies. N-acetylcysteine substantially increased survival when added at 10 mM concentration.