Estrogen and the estrogen receptor (ER)alpha play an important role in the male reproductive tract and in fertility. Previous studies demonstrated that disruption of ERalpha function resulted in abnormal morphology of the testis and efferent ductules (EDs) of adult mice. However, the effect of a lack of a functional ERalpha during early postnatal development has not been determined. The present study is an evaluation of morphological changes effected by a lack of ERalpha in the male reproductive tract during the postnatal period. Age-equivalent wild-type and ERalpha knockout (alphaERKO) mice at 10, 18, 35 and 60 days of age after birth were used for morphological comparison of the testes and ED. Light microscopic examination of the testes of the alphaERKO mouse revealed a dramatic dilation of the rete testis as early as 10 days of age, premature lumen formation, reduced epithelial height and greatly dilated lumen of seminiferous tubules as early as 18 days of age. The proximal ED of the alphaERKO mouse showed lumen dilation, reduction of epithelial height and a decrease of nuclear height as early as 10 days of age. Similar, but somewhat less severe, morphological abnormalities were observed in the distal ED of the alphaERKO mouse. These results indicate that a lack of functional ERalpha leads to morphological changes of the testis and ED of the early postnatal developing mouse. Based on these observations, we conclude that ERalpha plays an important role in normal development of the testis and ED, not only during adulthood but also during the entire postnatal period and presumably during fetal development.