Meningitis and meningoencephalomyelitis caused by Listeria monocytogenes were experimentally established in mice. The pathological changes in brain and spinal cord resulting from the infection resemble those observed in man and domestic animals. The efficacy of 24 antibiotics in treating this experimental infection was determined. Minocycline and chlortetracycline were the most efficacious antibiotics followed by amoxicillin, which was 2- to 4-fold less active than the former. However, the acute toxicity of amoxicillin to the murine central nervous system was at least 10-fold lower than that of the tetracyclines. Since parenteral amoxicillin may be of value in the management of listerial meningitis and meningoencephalomyelitis in man and domestic animals, clinical trials seem warranted.