In order to evaluate the early response of the alveolar epithelium following lung injury, male Long‐Evans adult rats (280–350 g) were treated with a single dose (30 mg/kg, ip) of the herbicide paraquat. No animal died during the 72 h that followed the acute administration of the herbicide. When compared to control, total lipid, phosphatidylcholine, and disaturated phosphatidylcholine contents of lung homoge‐nates from the paraquat‐treated rats were significantly reduced 48 h postdose (respectively 70, 24, and 37%). Comparatively, the total lung alkaline phosphatase activity was significantly reduced as early as 12 h postdose, and by 48 h the activity had decreased by ∼50%. Although a significant decrease in total lung acid phosphatase activity was observed 24 and 48 h after the treatment, the effect was much less than with the alkaline phosphatase activity (15% versus 50%, respectively). The lysosomal β‐N‐acetytglucosaminidase and the cytoplasmic lactate dehydrogenase activities were not affected by the herbicide treatment. A subcellular fractionation of the treated lungs showed that 48 h postdose, the total alkaline phosphatase activities associated with lamellar body and surfactant fractions were decreased respectively by 60% and 49%. Due to the intrinsic association of a strong alkaline phosphatase activity with the pulmonary surfactant system, these data suggest that the monitoring of the alkaline phosphatase activity in lung fractions could represent an early and sensitive indicator of toxicity to the alveolar epithelium, most probably to type II cells.