We have previously shown that cyclosporin A (CsA), an inhibitor of protein phosphatase 2B (calcineurin), attenuates hyperoxia-induced reductions in murine lung compliance. CsA protected against hyperoxia-induced changes in neutrophil infiltration, capillary congestion, edema and hyaline membrane formation. Gene expression studies were conducted in order to identify the gene expression patterns underlying the protective effects of CsA during hyperoxic lung injury. After 72 hours of simultaneous treatment with >95% oxygen and cyclosporin A (50mg/kg/day), RNA was isolated from murine lungs. RNA from treated and untreated lungs was reverse transcribed to cDNA, competitively hybridized and used to probe 8,734 complimentary DNAs on the Incyte mouse GEM1 array. Several known genes and expressed sequence tags showed increased (Gen Bank accession numbers : AA125385, AA241295, W87197, syntaxin and cyclin G) or decreased (AA036517, AA267567, AA217009, W82577, uteroglobin, stromal cell derived factor 1 and surfactant protein C) expression after hyperoxia. Hyperoxia-stimulated reductions in surfactant protein C (SP-C) gene expression were confirmed through Northern blot analysis. The increase in gene expression of one expressed sequence tag (AA125385) with hyperoxia was reversed by CsA treatment. Sequence data demonstrated that this expressed sequence tag (EST) has high homology to murine cyclin B1. Western blot analysis did not demonstrate any changes in distal lung cyclin B1 expression after hyperoxia. Protein expression of cyclin B1 in the distal lung was observed in the endothelial cells, bronchiolar epithelial cells, and both the type I and type II alveolar epithelial cells. Further analysis of cyclin B1 may elucidate the protective actions of CsA in hyperoxic injury.