Research has long supported the view that the brain is immunologically privileged, in part because normal, uninfected neurons were not thought to express major histocompatibility complex (MHC) class I molecules. Recently, however, it has been shown that neurons normally express MHC class I molecules in vivo. Furthermore, accumulating evidence indicates that neuronal MHC class I does not simply function in an immune capacity, but is also crucial for normal brain development, neuronal differentiation, synaptic plasticity and even behaviour. These findings point to new directions for research, and imply that immune proteins could be involved in the origin and expression of neurological disorders.