Discussion and summary The agent isolated by Chandler in mice inoculated intracerebrally with brain tissue from goats affected with experimental scrapie can be passed serially in mice by this route. In the Rocky Mountain Laboratory stock of Swiss mice it causes a relentlessly progressive, and invariably fatal, disease of the central nervous system, usually after an incubation period of 4 to 5 months. The disease is characterized clinically by incoordination of gait, muscular atrophy, and drowsiness and neuropathologically by prominent astrocytosis, degeneration of neurons, and spongy alteration of the neuroparenchyma. That the agent causing this disease in mice is the transmissible agent of scrapie may be questioned. At present, identification of the scrapie agent can be made only by observing its pathogenic capacity in susceptible sheep and goats. In these hosts it induces a distinctive clinicopathologic picture whose essential features also characterize the infection in mice. Thus, the long incubation period, the slowly progressive course of the disease, and the degenerative changes in the central nervous system all are consistent with the view that the agent under study is the transmissible agent of scrapie. Moreover, first passage mouse brain has induced scrapie in goats inoculated intracerebrally(4). At this laboratory, goats inoculated intracerebrally or subcutaneously with a 10-1 suspension of fourth passage mouse brain have been observed for too brief a period (5 months) to permit any conclusion about the ability of this inoculum to cause typical caprine scrapie. The high concentrations of the agent in the brain, spinal cord, spleen, and thymus of affected mice make it appear unlikely that a toxic substance is being passed. That the agent passes through a gradacol membrane of 100 mμ average pore diameter, but not one of 30–100 mμ, suggests it is a medium-sized virus.