The serum transmissibility of immune polioencephalomyelitis in C58 mice was characterized. The disease could be transmitted in C58 mice 10 or more months old but not in the BALB/wm, C3H/HeJ, C57BL/6J and AKR/J strains. The serum of both young and old mice was positive 24 hr after they were immunized with line Ib malignant leukocytes, reached a high titer (1:10,000) and remained positive for 11 to 15 days. Young mice remained free of disease. The active serum component was resistant to RNAse, DNAse and phosphodiesterase but was essentially inactivated by pronase. Sequential exposure of serum to RNAse or DNAse followed by pronase did not inactivate the serum factor more effectively than pronase alone. Transmission studies with purified immunoglobulins and immunoabsorption tests indicated that the serum factor was not an immunoglobulin. The active serum component was resistant to 37°C for 4 hr, repeated freeze-thaw, but was inactivated by exposure to 56°C for 45 min. Ultrafiltration studies showed that the active serum factor had a molecular weight between 64,000 and 165,000.