Electrophoretic mobility shift assays revealed minimal levels of NF-κB activity in rat distal lung epithelial cells cultured at fetal (23 mmHg) or adult alveolar (100 mmHg) PO 2 , but revealed significant activation of this transcription factor in cells exposed to a rise in PO 2 mimicking that experienced at birth. This response was entirely abolished by pretreating cells with 5 mM sulfasalazine (SSA). This shift in PO 2 also evoked a rise in apical Na + conductance (GNa + ) that may underlie the O 2 -evoked stimulation of Na + transport seen in these cells. Pretreatment with SSA had no effect upon GNa + in cells cultured continually at adult or fetal PO 2 but did inhibit the increase in GNa + seen in cells that had experienced the rise in PO 2 . O 2 -evoked activation of NF-κB may thus mediate the increased Na + transport that occurs when the distal lung epithelial cells are exposed to a physiologically-relevant increase in PO 2 .