THE induction of oxytocin receptor (OTR) synthesis in the periphery and in the brain by estrogen is critical for reproductive success. Oxytocin receptors are involved in the control of parturition, milk ejection, and sexual and maternal behaviors. The discovery of a second estrogen receptor (ERβ) in the brain and the failure ofin vitrotranscription studies using OTR promoter constructs to replicate thein vivotranscriptional regulation have raised questions regarding the molecular mechanisms involved in the regulation of the OTR gene by estrogen. Using mice genetically deficient in estrogen receptor a (ERα), we demonstrate that ERα is not necessary for basal OTR synthesis, but is absolutely necessary for the induction of OTR binding in the brain by estrogen.