Horses which had passed a few months to a few years asymptomatically after the last recurrence of equine infectious anemia (EIA) showed a typical febrile response after treatment with the immunosuppressive agent, dexamethasone (DM) or cyclophosphamide (CY). In horses showing a febrile response, EIA virus which had not been neutralized by neutralizing antibody previously produced was propagated. In DM-treated horses it disappeared from the blood soon after pyretolysis and antibody against the virus was produced promptly. In contrast, detectable viremia persisted in CY-treated horses for 10 to 84 days after pyretolysis. Antibody against the virus was barely produced for 42 to 126 days after treatment. After drug treatment, there was no decrease in neutralizing antibody previously produced. Then, it was inferred that this febrile response was due to propagation of an immunologically variant virus which might have been produced as a result of decline in cell-mediated immunity. The role of cellular mechanisms in the development of immunity to EIA was also discussed.