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We investigated the involvement of endothelin B receptor signals in the activation of astrocytes in vitro and in vivo. Endothelin reversed the stellate morphology of astrocytes induced by several agents. Endothelin stimulaltes astrocytic stress fiber formation. This effect of endothelin is Ca 2+ -independent and mediated by rho protein signal cascades linked to tyrosine phosphorylation. Injection of endothelin into striatum caused reactive astrocytosis which is prevented by a systemic injection of endothelin B receptor antagonist. We propose the role of endothelin B receptor signal transduction in reactive astrocytes.