Epithelial remodeling in the rat pineal during fetal development was immunohistochemically analyzed by using antibodies for laminin and cadherin as molecular markers of basal lamina and intercellular junctions, respectively. The proliferation and differentiation of pinealocytes were also investigated in relation to the advance of epithelial remodeling. The pineal anlage of embryonic day 16 is completely covered by basal lamina immunolabeled for laminin. After embryonic day 17, local dissolution of the basal lamina occurs on the epithelial folds, which develop predominantly in the rostral pineal wall. Some pineal cells migrate through these interruptions and form cellular aggregations outside the basal lamina. Cadherin immunostaining reveals focal dissolution of intercellular junctions in epithelial regions protruding into the pineal lumen. Dissolution of the basal lamina and intercellular junctions accompanied by cellular migration into the stromal tissue or into the pineal lumen continues until birth. The distribution of mitotic cells immunolabeled for BrdU is homogeneous throughout the organ during the fetal period, whereas that of differentiating pinealocytes immunoreactive for synaptophysin shows striking regional heterogeneity in close correlation with the remodeling of the pineal epithelium. The migrating cell populations located either outside the basal lamina or inside the pineal lumen are more liable to become synaptophysin-positive than the rest of the epithelium. These results suggest that epithelial remodeling in the fetal pineal is induced, at least in part, by epithelial infolding and that this remodeling promotes the differentiation of pinealocytes.