The polyamines putrescine, spermidine and spermine have been linked to various processes of proliferation and differentiation of many cell types. Ornithine decarboxylase (ODC), the enzyme responsible for putrescine formation and probably the rate-limiting step in polyamine biosynthesis, may fulfill an important growth regulatory role. ODC activity is induced by a wide variety of factors. Our research goals are to study the mechanisms by which retinoids, phorbol esters, epidermal growth factor (EGF) and serum control proliferation of airway epithelial cells in culture. We have observed a rapid enhancement in ODC activity by phorbol esters, serum and EGF. This induction of ODC is inhibited by retinoids. We try to understand (1) how phorbol esters and retinoids effect ODC induction and whether their binding proteins or receptors are involved in this action, (2) whether prostaglandin synthesis is responsible for the induction by phorbol esters and the importance of prostaglandins in the control of cell growth, (3) to what extent the ODC activity correlates with proliferation and (4) the role that control of cell proliferation may play in cellular differentiation.