A number of sulfated polysaccharides were tested for their ability to inhibit passively induced experimental allergic encephalomyelitis (EAE) in rats. Heparin and fucoidan both completely inhibited passive EAE even when treatment was begun 3 days after transfer of cells. Pentosan sulfate was partially inhibitory whereas chondroitin-4-sulfate had no effect. Inhibition was not merely due to killing of the cells since active sensitization 14 days after cell transfer resulted in an early onset of disease indicating the persistence of transferred cells as memory cells. Although all the inhibitory polysaccharides are anticoagulants, it would appear that this function alone is not the reason for inhibition since a heparin preparation devoid of anticoagulant activity also partially inhibited EAE. Actively induced EAE was also significantly delayed by treatment with heparin. The results are discussed in terms of the polysaccharides inhibiting the enzymatic dependent movement of lymphocytes across central nervous system vascular endothelium.