Neurofibromin, the product of the neurofibromatosis 1 (NF1) gene, is an important tumor suppressor protein expressed most abundantly in the nervous system. Within the central nervous system, neurofibromin has been localized to neurons and oligodendrocytes but not astrocytes. As individuals with NF1 are at an increased risk for optic pathway gliomas and astrocytomas, we chose to re-evaluate the level of neurofibromin expression in primary cultures of murine cortical astrocytes under control and reactive conditions. Astrocytes under control conditions expressed low levels of NF1 mRNA and protein. Following stimulation with dibutyryl-cyclic AMP or interferon-gamma in combination with either lipopolysaccharide or interleukin-1 beta, there was a marked increase in NF1 mRNA and protein expression. These results suggest that neurofibromin may be involved in the process of reactive astrocytosis seen in response to CNS injury.