Lung damage in mice exposed to hyperbaric oxygen was assessed by measurement of wet and dry lung weights. The clinically useful thiol compound, N-acetylcysteine (NAC), which is known to maintain tissue levels of reduced glutathione, was found to protect lungs of mice compressed to 445 and 515 kPa oxygen for 30 min. NAC was administered intraperitoneally and the optimal conditions found to be 400 mg/kg 15 min-1 hr before compression. The antineoplastic agent bleomycin, which frequently causes life-threatening lung damage, was administered intratracheally (5 mg/kg), and potentiated lung damage caused by hyperbaric oxygen (445 kPa). NAC effectively protected the lungs of mice exposed to the combined deleterious effect of bleomycin and hyperbaric oxygen.