L cells persistently infected with strain Armstrong lymphocytic choriomeningitis virus generated a variant which failed to develop the lethal neurologic disease after application to the brain. This virus was able to protect mice from the fatal consequences when inoculated intra-cerebrally prior to challenge with wild-type (wt) virus. After infection of mice with the attenuated variant and thereafter with the wt virus, production of the latter was extraordinarily reduced. As expected, virus elimination was finally achieved by cytotoxic T lymphocytes, whose activation was accelerated. Furthermore, two events seem to play an important part in this enhanced virus reduction. First, from the beginning of the infection with wt virus, neutralizing antibodies could be noticed. The second observation was an excessive production of interferon-α 1 day after the challenge infection