We have studied the effect of rat central nervous system (CNS) neurons on the inducibility of major histocompatibility complex (MHC) class I molecules on syngeneic astrocytes. In a co-culture system composed of embryonic rat cortical neurons and neonatal astrocytes, intact neurons decreased constitutive expression of MHC class I determinants and inhibited the induction of class I products on astrocytes. Viability of the neurons and direct contact with astrocytes was critical for this effect. Soluble factors released by neurons were inefficient. Our data indicate that the lack of MHC class I expression on astrocytes in situ might be the result of an active suppression mechanism rather than merely due to the absence of activating factors in the CNS.