Interferon-gamma (IFN-gamma) is a cytokine mainly secreted by activated T-lymphocytes. Treatment of mouse astrocytes in vitro with IFN-gamma augmented the basal expression of the primary response proto-oncogenes c-myc and L-myc as detected by Northern blotting. Such inductions were maximal at doses of 10 U/ml and after 60 min of treatment. Astrocytes fully differentiated in vitro do not express N-myc mRNA nor are induced to express it by exposure to IFN-gamma. As demonstrated by flow cytometry, the common protein product of the myc family was present in the nucleus of the cells. The specificity of IFN-gamma induction was demonstrated when antibodies against IFN-gamma completely suppressed the overinduction of these mRNAs. No apoptotic death can be detected in astrocytes treated with IFN-gamma at doses that induce c-myc expression. Conversely, treatment with a dose of 10 U/ml induced cells proliferation in astrocytic cells as measured by (3)H-thymidine incorporation.