For the study of malignant glioma, we have previously characterized a highly tumorigenic murine astrocytoma, SMA-560, which arose spontaneously in an inbred, immunocompetent VM/Dk mouse. Using this cell line as a model of murine glioma, we performed DNA microarray analysis of autologous normal murine astroctyes (NMA) and SMA-560 tumor cells grown in monolayer culture or intracranially in syngeneic immunocompetent or immunocompromised hosts in order to determine whether tumors grown in vitro recreate the complex genetic regulation that occurs in vivo. Our findings support our hypothesis that glioma phenotype in vitro may be quite different in vivo and significantly altered by in situ growth factors and other invading cell populations.