Direct exposure to poliomyelitis virus of the central end of a cut branch of the V cranial nerve was followed by centripetal spread of infection to the semilunar (Gasserian) ganglion, involvement of which was detected both histologically and by subinoculation as early as the 3rd day. In some instances infection did not progress further; in others it spread into the CNS with initial involvement of the trigeminal centers in the pons and medulla as early as the 4th day and by the 5th day was further advanced but still limited to the brainstem. Once infection was established it progressed both rostrally and caudally, at times with great rapidity, through the brainstem and reached the cord on the 6th or a later day. Incidental exposure in traumatized muscle of peripheral fibers of the VII motor nerve led in some instances to spread along that pathway directly into the CNS. Application of the experimental results to human poliomyelitis is of interest chiefly in four respects. (1) The ascent of infection from a peripheral ganglion of the head area to the CNS with initial encephalitis of the brainstem and subsequent descent to the spinal cord is believed to parallel the evolution of the human disease as suggested by the character and order of development of the early symptoms and signs. (2) The failure in some instances of infection to spread from an infected peripheral ganglion to the CNS may parallel inapparent ("subclinical") poliomyelitis in man. (3) Invasion of virus through traumatized muscle directly to the CNS also has possible analogues in human experience which will be discussed in a later paper. (4) The presence of well marked and sometimes extensive lesions in the brainstem one or more days before symptoms emerge is also believed to parallel the human case.