Treatment of scrapie-infected mice with dextran sulphate (DS) 500 resulted in considerably reduced spleen titres over a long period of time. Subsequently, the central nervous system disease was delayed or even prevented during the 350-day period of observation. Both effects increased after multiple injections of the compound. The potency of DS 500 to protect against scrapie was greatest when treatment and infection were carried out simultaneously. Under these conditions the lethality of 500 to 1000 LD50 was reduced to almost zero. Treatment as early as 10 weeks before infection still prolonged the incubation periods. Of several other polyions tested, dextran sulphate 5 and pentosan polysulphate also impaired scrapie pathogenesis.