SUMMARY: Cellular components in homogenates of brain tissue from scrapieaffected mice have been separated by centrifugation in sucrose and caesium chloride density gradients with the objective of location of the scrapie agent and concentration of scrapie activity. Improvements in the relative activity of the fractions removed from sucrose gradients were small but recovery was high in the material sedimented through 0.88 M-sucrose. No peak of activity was observed in zones removed from a caesium chloride gradient and activity throughout remained strongly associated with particulate matter. Ultrasonic disruption had little effect on scrapie activity. Concentrated preparations of sufficient potency for characterization of virus particles by electron microscopy were not obtained. From various experimental evidence the scrapie agent, if a virus, appears to be of small size. The strong association of the agent with tissue debris suggests that the presence of a tissue component may be necessary in the experimental transmission of the condition.


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