Electrophoretic mobility shift assays revealed minimal levels of NF-kappaB activity in rat distal lung epithelial cells cultured at fetal (23 mmHg) or adult alveolar (100 mmHg) P-O2, but revealed significant activation of this transcription factor in cells exposed to a rise in P-O2 mimicking that experienced at birth. This response was entirely abolished by pretreating cells with 5 mM sulfasalazine (SSA). This shift in P-O2 also evoked a rise in apical Na+ conductance (G(Na+)) that may underlie the O-2-evoked stimulation of Na+ transport seen in these cells. Pretreatment with SSA had no effect upon G(Na+) in cells cultured continually at adult or fetal P-O2 but did inhibit the increase in G(Na+) Seen in cells that had experienced the rise in P-O2. O-2-evoked activation of NF-kappaB may thus mediate the increased Na+ transport that occurs when the distal lung epithelial cells are exposed to a physiologically-relevant increase in PO2.