Epithelial ovarian cancer (EOC) is the most common and lethal form of gynecological malignancy. These cancers are thought to be derived from the ovarian surface epithelium (OSE). We have previously reported that the epithelial-specific FGF receptor 2 splice variant IIIb is not expressed in normal OSE, but is expressed in approximately 80% of EOCs. We have examined the phenotypic effects of ligands to FGF receptor 2-IIIb, namely FGFs 1,7 and 10, on a panel of EOC cell lines. We show that these ligands increase cell viability, induce DNA synthesis, motility and chemotaxis and protect from spontaneous cell death when EOC cells are maintained in serum free medium. A blocking antiserum to FGF-7 reduces viability of 41-M EOC cells, and abrogates the ability of ascitic fluid containing FGF-7 to induce DNA synthesis in these cells. Finally, we show that FGF-7 can induce a reorganization of the actin cytoskeleton in SK-OV-3 ovarian cancer cells. It is suggested that ligands to FGF receptor 2-IIIb affect a range of phenotypes important in the neoplastic growth of EOCs.