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In addition to regulating estrogen receptor-dependent gene expression, 17β-estradiol (E₂) can directly influence intracellular signaling. In primary cultured cerebellar neurons, E₂ was previously shown to regulate growth and oncotic cell death via rapid stimulation of ERK1/2 signaling. Here we show that ERK1/2 signaling in the cerebellum of neonatal and mature rats was rapidly responsive to E₂ and during development to the environmental estrogen bisphenol A (BPA). In vivo dose-response analysis for each estrogenic compound was performed by brief (6-min) intracerebellar injection, followed by rapid fixation and phosphorylation-state-specific immunohistochemistry to quantitatively characterize changes in activated ERK1/2 (pERK) immunopositive cell numbers. Beginning on postnatal d 8, E₂ significantly influenced the number of pERK-positive cells in a cell-specific manner that was dependent on …