Amnion epithelial and mesenchymal cells were separated by differential protease treatment, and the separated cells were maintained in monolayer culture. Keratinocyte growth factor (KGF) messenger RNA (mRNA) was readily detected by Northern analysis of amnion mesenchymal cell total RNA (10 micrograms) but not in amnion epithelial cells. Treatment of the amnion mesenchymal cells in serum-free medium with tetradecanoyl phorbol acetate (1 nM) caused an increase in the level of KGF mRNA. Forskolin treatment also caused an increase in KGF mRNA but not to the levels attained with tetradecanoyl phorbol acetate treatment. Dexamethasone (1 nM) treatment of these cells effected a reduction in the level of KGF mRNA. Prolonged maintenance of mesenchymal cells in serum-free medium also was associated with an increase in the level of KGF mRNA. Treatment with a variety of other agents, viz., interleukin (IL)-1, IL-6 plus or minus IL-6 soluble receptor, IL-11, oncostatin M, epidermal growth factor (EGF), and transforming growth factor-beta and not modify the level of KGF mRNA. Treatment of amnion epithelial cells with KGF caused an increase in the rate of [3H]thymidine incorporation, but the rate of cell replication induced by KGF was less than that induced by treatment with EGF. Transforming growth factor-beta treatment inhibited basal and EGF- and KGF-stimulated amnion epithelial cell replication. The findings of this study are indicative the KGF is expressed in human amnion mesenchymal cells, and that KGF may act on the epithelial cells of this tissue.