Recent evidence that astrocytes can be induced to express the class II major histocompatability (MHC) antigens suggests that these cells may be involved in the development of intracerebral immune responses. The principal inducer of MHC class II antigen (Ia) expression is a soluble lymphokine, gamma-interferon (gamma-IFN). Normally astrocytes do not express significant levels of Ia antigens despite the fact that agents such as gamma-IFN may be present in the central nervous system (CNS). Here we report that a major neurotransmitter, norepinephrine (NE), inhibits, in a dose-response fashion, the ability of gamma-IFN to induce Ia antigen expression on cultured astrocytes derived from newborn BALB/c mice. This finding may indicate that the brain contains inhibitory modulators that serve to prevent the up-regulation of intracerebral immune responsiveness.