Exposure of the lung to elevated oxygen leads to structural and cellular injury followed by extensive tissue remodeling. In vitro models utilizing isolated cells exposed to hyperoxic conditions or exogenously added oxidants may be injurious or stimulatory depending on the specific cell type and level and duration of exposure. In the present study, proliferation of cultured rat tracheal smooth muscle cells was inhibited by oxygen concentrations of 40 and 70% compared with a "normoxic" concentration of 21%. Exposure to 70% oxygen had a hypertrophic effect on the cells, as indicated by increased cellular protein content, whereas cells exposed to 21% oxygen did not show increased protein content. Exogenously added oxidant, H2O2, resulted in complete inhibition of growth of tracheal smooth muscle cells at concentrations > 3 microM. Much higher concentrations of H2O2 were required to inhibit proliferation of vascular smooth muscle cells and rat lung fibroblasts. The heightened sensitivity of airway smooth muscle cells to oxygen and oxidants may be an important factor in the early events following hyperoxia-induced lung injury.