The ability of estrogen to modulate the expression of ventral and dorsal striatal dopamine receptors D1, D2, and D3 was examined in vivo using semi-quantitative in situ hybridization and ligand binding autoradiography. Two-week treatment with subcutaneous pellets of 17β-estradiol (25 mg) downregulated D2 dopamine receptor mRNA in both dorsal and ventral striatum (shell and core regions of nucleus accumbens). No significant changes in D1 or D3 mRNA expression were detected. Ligand binding autoradiography did not reveal changes in D1, D2, or D3 receptor protein expression. We also assessed the ability of 17β-estradiol to regulate D2 gene promoter activity in NB41A3 neuroblastoma cells that express this gene endogenously using co-transfections with an estrogen receptor expression vector. While a small fragment of the D2 promoter could be activated 2.5-fold by estrogen, a larger portion of the D2 gene was not regulated by this treatment. Estrogens do not appear to have a net effect on striatal dopamine receptor expression. The observed downregulation of D2 receptor mRNA in the dorsal and ventral striatum in vivo could be secondary to the increased striatal dopamine release induced by estrogen. Synapse 34:222–227, 1999. Published 1999 Wiley-Liss, Inc.