The etiological agent of genetically restricted, age-dependent poioencephalomyelitis of mice (the ADPE agent) and several isolates of lactate dehydrogenaseelevating virus (LDV) were compared by biological, physical-chemical, and antigenic criteria. The data indicate that the ADPE agent is a strain of LDV. Like LDV, the ADPE agent induced a selective elevation of plasma enzymes and splenomegaly in mice. The enzyme-elevating activity and the paralytogenic activity of the ADPE agent preparations were shown to belong to the same virus. The ADPE agent demonstrated LDV-like replication kinetics in vivo and in vitro. Moreover, the ADPE agent required primary mouse macrophages for in vitro replication, as does LDV. In turn, the LDV isolates induced a paralytic disease with ADPE-like lesions in the spinal cords of immunosuppressed C58 mice. However, the LDV isolates showed a stronger dependence on strain and age of mouse for the induction of paralysis than did the ADPE agent. The LDV isolates and the ADPE agent exhibited indistinguishable morphologies, buoyant densities, structural protein patterns, and virion ribonucleic acid sedimentation rates. Furthermore, they displayed strong antigenic cross-reactivity, as determined by cross-protection in vivo and by radioimmunoassay.MATERLkIS AND METHODS Mice. C58/Wm mice (obtained from W. H. Murphy, The University of Michigan, Ann Arbor, Mich.) and AKR.M/nSn mice (obtained from the Jackson Laboratory, Bar Harbor, Maine) were maintained for Merck & Co. by Buckshire Corp., Perkasie, Pa. Swiss Albino mice were purchased from Lab Supply, Indianapolis, Ind. AKR/J, C3H/HeJ, CBA/J, and SJL/J mice were purchased from the Jackson Laboratory.