Differentiated neurons in several brain regions express the retinoblastoma (Rb) tumor suppressor gene. Changing the tumor suppressor function of Rb by expressing transcription factor E2F1 and viral oncoprotein E1A in cerebellar granular neurons in vitro and in cerebral cortical neurons in vivo results in the induction of DNA synthesis in these neurons. Immunoliposome-mediated transfection of E1A and E2F1 cDNAs into the adult cortical neurons of rats in vivo results in initiation of DNA synthesis in 5-15% of the transfected neurons. These results indicate that expression of Rb may be necessary to prevent induction of differentiated neurons to proliferate since many mitogenic growth factors are expressed in the brain.