The effect of hypoxia on the development of bleomycin lung toxicity was studied in 26 rats. Thirteen rats received an endotracheal injection of saline, and 13 rats received a similar injection of 1.5 units of bleomycin in saline. Six saline-treated and 6 bleomycin-treated rats were exposed to 10% oxygen for 2 days prior and 2 days subsequent to the injections, and then breathed air for a further 5 days before being killed. The other rats breathed air continuously, and were also killed 7 days after the injections. Although all bleomycin-treated animals had some evidence of lung toxicity, histologic examination of the lungs revealed markedly reduced bleomycin toxicity in the rats exposed to hypoxia. This was confirmed by morphometry, which demonstrated that the volume density of alveolar walls (mean +/- SEM) was significantly lower in the bleomycin-hypoxia group (11.8 +/- 0.8%) than in the bleomycin-air group (18.8 +/- 1.1%) (p less than 0.001). It is concluded that hypoxia offers protection against bleomycin lung toxicity in the rat.