Lung cancer is the leading cause of cancer death in men and women in the United States. The cyclooxygenase pathway has a role in colon cancer chemoprevention and a potential role in lung cancer. Cyclooxygenase inhibition reduces lung cancer multiplicity in a murine model. We have shown that prostacyclin synthase (PGI2S) overexpression protects against tumor development in a transgenic mouse model. We hypothesize that eicosanoid balance is of importance in lung tumorigenesis, and propose a model for transcriptional regulation of PGI2S.