Cadherins are a family of cell surface molecules mediating calcium-dependent cell-cell adhesion in a variety of tissues. More than a dozen cadherins are expressed in the vertebrate brain. To obtain insight into the biological significance of this diversity in cadherin expression, we mapped the expression of N- and R-cadherin in the brain of the developing chicken embryo (days 2-19 of incubation) by immunohistochemical and in situ hybridization techniques. Whereas the expression of N- and R-cadherin is relatively uniform or weak in early (about 2-5 days of incubation) and late development (15 days of incubation to hatching stage), these two molecules are differentially expressed in specific nuclei and fiber tracts between days 6-11 of incubation. For example, in the mes- and diencephalon, one of the tectofugal pathways and its target nuclei, here called the tecto-pretecto-rotundal system, express N-cadherin. R-cadherin is expressed by a different tectofugal system, the tectoisthmic pathway. The other tectofugal systems express neither N- nor R-cadherin. In addition, a small number of other mes- and diencephalic nuclei express N- or R-cadherin. On the basis of these results and experimental evidence from other studies, we speculate that the two cadherins are involved in the formation and segregation of particular functional systems within the vertebrate central nervous system (CNS) by regulating the formation of nuclei, and the pathfinding and/or the selective fasciculation of neurites. Apart from neuronal elements, a variety of vascular and ependymal structures also express N-cadherin or R-cadherin, e.g., the parenchymal blood vessels, the choroid plexus, the floor and roof plates, and the ventricular lining. These findings suggest that the two cadherins play a variety of roles during the development of neuronal and nonneuronal epithelial structures throughout CNS development.