The ability of hypoxia (PO2 57 Torr) and anoxia (PO2 0 Torr) to induce the release of histamine or sulfidopeptide leukotrienes from dispersed porcine parenchymal lung cells was examined. Spontaneous release of histamine (9.2 +/- 1.3%) was not significantly increased during hypoxia or anoxia, and spontaneous leukotriene release was not detected under any conditions. The release of leukotriene induced by A23187 (78 +/- 11 pmol leukotriene D4 equivalent/10(7) parenchymal lung cells) was unchanged during hypoxia and was significantly reduced (55.4 +/- 7.7% control leukotriene release) during anoxia, whereas A23187-induced histamine release (63.2 +/- 4.2% total cell histamine) was unaffected by reduced oxygenation. Reduction of final buffer pH from 7.4 to 7.0 did not affect mediator release. High-pressure liquid chromatographic analysis of the released leukotrienes revealed a mixture of leukotrienes C4 and D4, with a symmetrical reduction in product during anoxia. Although leukotriene release in response to hypoxia was not demonstrated, the findings do not preclude limited local release of leukotrienes, perhaps in association with increased smooth muscle responsiveness.