We investigated whether neutrophil suppression would prevent the early hyperoxic injury to the rabbit alveolar epithelium. Rabbits received a single intravenous injection of either nitrogen mustard (2 mg/kg) or saline and were exposed to 100% O2 for 64 h. At the end of the hyperoxic exposure, there were 20 ± 7 neutrophils/ml blood in the nitrogen mustard group vs. 5,935 ± 1,174 in the control group (means ± SE; P < 0.05). The corresponding numbers in lung extravascular tissue, expressed per high-power field, were 0.37 ± 7 and 5.9 ± 0.35, respectively (P < 0.05). At this time, the rate constants of solute flux for 57Co-vitamin B12 (r = 6.5 Å) and 131I-cytochrome c (r = 17 Å), across the alveolar epithelium, were 33 ± 5 (min-1) and 7 ± 2 for the nitrogen mustard and 29 ± 5 and 6 ± 1 for the saline group, respectively. These variables were ninefold higher than their corresponding values in animals breathing air. We concluded that neutrophils do not play a significant role during the early stages of sublethal hyperoxic injury to rabbit alveolar epithelium.