We set out to determine whether or not the "mucolytic" drug N-acetylcysteine would speed the reversal of cigarette smoke-induced secretory-cell hyperplasia to normal, similar to that found previously for two nonsteroidal antiinflammatory drugs. Cigarette smoke alone significantly (p less than 0.01) increased the number of secretory cells in seven out of eight airway levels studied and maintained a significant increase in five of the levels at least 3 weeks after cessation of exposure. Treatment of rats with N-acetylcysteine, as 1% of their drinking water during the recovery period, reduced the time taken for secretory cell number to return to normal to between 4 days and 3 weeks, depending on airway level.