This study investigated whether hypoxia affected the expression of mitochondrial manganese-containing superoxide dismutase (Mn-SOD) and the cytosolic copper and zinc-containing superoxide dismutase (Cu,Zn-SOD) in alveolar type II epithelial (ATII) cells and lung fibroblasts. Cells were exposed in vitro to air (controls) or to 2.5% oxygen (hypoxia) for 24 h. Mn-SOD and Cu,Zn-SOD mRNA expression was measured by quantitative reverse transcriptase-polymerase chain reaction. Both Mn-SOD and Cu,Zn-SOD mRNA expression in ATII cells decreased significantly after 1 day in hypoxic conditions. The decrease in Mn-SOD mRNA (-69%) was greater than that in Cu,Zn-SOD mRNA (-48%). ATII cell surfactant protein A transcript expression remained constant. Mn-SOD (-52%) and Cu,Zn-SOD (-54%) mRNA expression decreased similarly in lung fibroblasts cultured during hypoxia. The half-life of the Mn-SOD mRNA measured in lung fibroblasts exposed to air or hypoxia for 24 h decreased significantly from 5.8 +/- 0.1 to 3.8 +/- 0.7 h (-34%). The half-life for the Cu,Zn-SOD decreased significantly from 4.0 +/- 0.3 to 2.4 +/- 0.1 h (-40%). Neither Mn-SOD nor Cu,Zn-SOD protein expression in ATII cells changed significantly during hypoxia. Hypoxia decreases expression of Mn-SOD and Cu,Zn-SOD mRNA in ATII cells and lung fibroblasts in part by decreasing stability of the mRNA transcripts.