Activated human neutrophils (PMNs) were demonstrated to inhibit total de novo phosphatidylcholine (PC) synthesis in monolayered rat alveolar type II cells (T2C). Non-activated PMNs had no effect on PC synthesis in this system. The magnitude of inhibition T2C PC synthesis by phorbol myristate acetate-activated PMNs in six experiments averaged 59.0 +/- 13%. Exogenous chelated iron (ferric pyrophosphate) did not appear to augment the PMN-mediated inhibition of T2C PC production in this model. Alpha-1-antiprotease usually provided no protection relative to the PMN insult towards the T2C. However, superoxide dismutase and catalase alone or in combination generally provided a significant, protective effect. Although activated PMNs consistently decreased T2C PC synthesis, this effect did not appear to involve generalized T2C cytotoxicity, as assessed by lack of release of cytosolic lactate dehydrogenase. These results indicate that PMNs can inhibit T2C PC synthesis in vitro, probably via oxyradical injury. This type of pulmonary host autoinjury may be operative in a variety of acute lung injury syndromes involving pulmonary sequestration of activated PMNs.