The distributions of five NMDA receptor channel subunit mRNAs in the mouse forebrain at postnatal day 21 were semiquantitatively examined by in situ hybridization with subunit-specific oligonucleotide probes. In contrast to ubiquitous distribution of the zeta 1 subunit mRNA throughout the forebrain, distributions of four epsilon subunit mRNAs were highly variable from nucleus to nucleus. The telencephalon (except for the septum) expressed the epsilon 1 and epsilon 2 subunit mRNAs. Various combinations of the epsilon 1, epsilon 2, epsilon 3, and epsilon 4 subunit mRNAs were present in different nuclei of the septum, the olfactory bulb, and the thalamus. In the hypothalamus, the suprachiasmatic nucleus expressed distinct signals for the epsilon 3 subunit mRNA alone, whereas other nuclei showed faint signals for the epsilon 1, epsilon 2, and epsilon 4 subunit mRNAs. Moreover, different signal levels of the epsilon subunit mRNAs were found in various regions. The hippocampal CA1 region expressed higher signals for the epsilon 1 and epsilon 2 subunit mRNAs than the CA3 region and the dentate gyrus. In the cerebral cortex, signal levels of the epsilon 1 subunit mRNA were higher in the laminae II/III, IV, and VI than the lamina V, whereas those of the epsilon 2 subunit mRNA were highest in laminae II/III and lowest in laminae IV and V. Different signal levels between the epsilon 1 and epsilon 2 subunit mRNAs were also discerned in the amygdala, the caudate-putamen, and the thalamus. The distinct anatomical distributions and differential signal levels of the epsilon subunit mRNAs strongly suggest different subunit organizations of the NMDA receptor channel in different forebrain neurons, which may result in functional diversity of the channel in vivo.