PrP(Sc), an aberrantly folded protein, is the only identified component of the prion, an agent causing fatal neurodegenerative diseases such as scrapie and bovine spongiform encephalopathy. Dimethyl sulfoxide (DMSO) has been shown to reduce the accumulation of PrP(Sc) in scrapie-infected (ScN2a) cells, and to inhibit its aggregation in vitro. In humans, DMSO was used successfully in the treatment of various peripheral amyloidotic diseases. Here we show that administration of DMSO to scrapie-infected hamsters significantly prolonged disease incubation time, as well as delayed the accumulation of PrP(Sc) in Syrian hamster brains. Interestingly, administration of DMSO to scrapie sick hamsters resulted in increased clearance of protease-resistant PrP in their urine. We conclude that although DMSO by itself may not be sufficient to cure prion diseases, it may be considered as a component in a 'cocktail' drug approach for these disorders. Also, urine PrP testing should be considered for the assessment of treatment efficacy.