A single intraperitoneal injection of 250 micrograms dextran sulphate 500 (DS500) reduced the susceptibility of mice to scrapie given by the same route. A lower dose (25 micrograms) was less effective but still produced significant incubation period lengthening, while a high dose (2.5 mg) further increased the degree of prolongation. This reduced susceptibility occurred with DS500 administered up to at least 4 weeks prior to intraperitoneal scrapie inoculation and up to at least 2 weeks after scrapie inoculation. A reduced average effect, but more variable between mice, was obtained with DS500 given 1 month or 2 months after scrapie. The effective scrapie titre was reduced by 90% when DS500 was injected either 72 h before or 7 h after ME7 scrapie. Using a relatively lower but normally still fatal dose of the 22A strain of scrapie approximately 50% of the treated mice survived. The effective 90% loss of titre was consistent with either of these strains of scrapie in 11 different inbred strains of mice (BALB/c, BSC, BRVR, C3H, C57BL, IM, LM, MM, RIII, VL and VM). No significant increase in the prolongation effect was obtained using multiple DS500 doses in two different time combinations. DS500 causes long-term interference in both the early processing and the replication of scrapie agent, unlike those immunomodulators which increase susceptibility.