Major histocompatibility complex (MHC) class I genes consist of classical (Ia) and nonclassical (Ib) types. Recently, a set of structurally similar MHC class Ib genes in the rat, denoted RT1-U, was described. We here demonstrate expression of RT1-U mRNA using highly stringent oligonucleotide in situ hybridization in several different neuronal populations, including different motor nuclei and the substantia nigra in the rat MHC (c) and (n) haplotypes under normal conditions. The expression pattern for beta2-microglobulin mRNA was almost identical. In contrast, neuronal expression of classical MHC class I (RT1-A) was low. Interestingly, after mechanical nerve injury, glial cells predominantely upregulated expression of RT1-A, whereas neuronal expression of RT1-U remained unchanged. Neuronal expression of nonclassical MHC class I may thus be important for immune surveillance in the nervous system.