Bis (Bcl-2 interacting death suppressor), identified as a Bcl-2-binding protein, has been suggested to have diverse functions in addition to binding to Bcl-2, thereby regulating cell death. To investigate the potential role of Bis in the developing brain, the spatiotemporal expression of Bis protein was studied in the rat forebrain during prenatal and early postnatal development using immunohistochemistry. Initial expression of Bis was detected in the medial telencephalic wall of the lateral ventricle, the area most likely corresponded to the cortical hem from the earliest age examined (E13). There was an abrupt increase of immunoreactive neurons in the cortex and hippocampus during the first postnatal week, which declined thereafter. Two populations of Bis-immunoreactive neurons can be clearly distinguished in the developing forebrain: a population of differentiating and postmitotic neurons coexpressing Bis and microtubule-associated protein-2 (MAP-2), and a population of neurons with the characteristic morphology of Cajal-Retzius cells located exclusively in the marginal zone/layer I of the cortex and in the hippocampal equivalents of the marginal zone. The latter neurons were colabeled with reelin, a marker for Cajal-Retzius cells. While Bis expression in the cerebral cortex and hippocampus exists only transiently by P14, considerable expression was found to be maintained in the rostral migratory stream and the subventricular zone of the lateral ventricle, where Bis-immunoreactive cells were glutamine synthetase-positive glial cells. Our results suggest that Bis may contribute to the developmental processes, including the differentiation and maturation of specific neuronal populations in relation to Bcl-2 in the developing rat forebrain.