Surfactant protein A (SP-A) is an abundant glycoprotein in surfactant that is synthesized and secreted by alveolar type II cells and likely has important roles in mediating surfactant function and metabolism. In the present study, we demonstrate that exposure to 85% oxygen increased alveolar lavage and lung SP-A, and that these increases were related to increased SP-A synthesis and mRNA. Adult rats were exposed to room air or to 85% oxygen for 3, 5, or 7 days. Continuous exposure to hyperoxia progressively increased SP-A content, with a 20-fold increase in alveolar lavage and a 10-fold increase in lung SP-A content observed after 7 days. SP-A-specific mRNA increased in the lungs of rats exposed to oxygen, occurring with a time course similar to the increase in tissue SP-A. SP-A mRNA was increased 7-fold after 7 days of oxygen exposure. Synthesis of SP-A was increased 2- to 3-fold and secretion was increased 6- to 7-fold by type II epithelial cells isolated from oxygen-exposed rats. We conclude that exposure to hyperoxia increased lung and alveolar SP-A pool sizes. Increased expression of SP-A was related, at least in part, to increased SP-A mRNA and increased SP-A synthesis and secretion by type II epithelial cells.