To understand the role of tyrosine kinases in regulation of astrocyte morphology, we investigated the effects of tyrosine kinase inhibitors on morphology of cultured rat cortical astrocytes. Cultured astrocytes exhibited flattened, polygonal morphology in the absence of stimulation, but changed into process-bearing stellate cells in the presence of the tyrosine kinase inhibitor genistein (3-100 microM). Genistein-induced astrocyte stellation was abolished by treatment with colchicine or paclitaxel, indicating the involvement of cytoskeletal elements. The effect of genistein was mimicked by another tyrosine kinase inhibitor herbimycin A, but not by daidzein, an inactive analog of genistein. These results suggest that tyrosine kinases are in an activated state in the absence of stimuli and contribute to the maintenance of polygonal morphology of cultured astrocytes.