The effect of genetic immunization of neonatal mice was tested with a plasmid vector expressing the rabies virus glycoprotein. Mice inoculated within 24 hr after birth with the plasmid DNA developed antibodies as well as T helper cells to the rabies virus glycoprotein. The response could not be distinguished from that seen upon vaccination of adult mice. Taken together, these data clearly show that the immune system, known to be prone to induction of immunological tolerance to some antigens applied during the early neonatal period, can readily respond to rabies virus glycoprotein induced by a plasmid vector.