We have compared the effects of N,N-dimethylformamide (DMF) and transforming growth factor (TGF)-beta 1 on the growth and phenotype of HOC-7 ovarian cancer cells. Previous density gradient fractionation of untreated HOC-7 cells suggested that rapidly growing small polygonal medium density cells revert spontaneously into less malignant flattened low density cells. Here we demonstrate that DMF and TGF-beta 1 induce similar flattened cell phenotypes. Both agents induce qualitatively similar alterations in the cells. DMF, however, exerted stronger effects than TGF-beta 1. The cells become flattened, develop cytoplasmic extensions, and reduce DNA-synthesis as well as anchorage-dependent and -independent growth. These effects are reversible after removal of the inducers, indicating that the cells have not become terminally differentiated. Electron microscopy demonstrates prominent filament bundles in treated cells. Immunofluorescence further shows that these cells contain large amounts of cytokeratin. Immunocytochemistry and ELISA demonstrate 1- to 5-fold higher amounts of desmoplakin and fibronectin after DMF- or TGF-beta 1-exposure. The described differentiation-like responses of HOC-7 cells can be used for recognition of pharmacologically induced maturation of ovarian cancer cells.