Treatment of rats with a developing or an established lesion of experimental allergic encephalomyelitis (EAE) with mitoxantrone (Novantrone) suppressed the hind limb paralysis associated with the disease. Histopathological examination of the spinal cords of these rats showed that mitoxantrone-treated rats had reduced vascular lesions that are associated with EAE. Spleen cells derived from immunized rats that had been treated in vivo with mitoxantrone did not transfer disease when these cells were administered to naive syngenic recipients. In addition, spleen cells from diseased rats did not transfer EAE lesions when these cells were administered to recipients that had been treated with mitoxantrone. Recipients treated with mitoxantrone were resistant to EAE lesions induced by sensitized cells in a rapid passive transfer system. Finally, when spleen cells from rats with EAE were incubated, in vitro, with mitoxantrone, these cells did not transfer disease to recipients. Thus the present studies indicate that treatment with mitoxantrone can suppress the lesions associated with both the active and passive forms of EAE.