We compared patients with subacute sclerosing panencephalitis who received treatment according to our protocol for at least 6 months (19 patients) with the patients who could not receive any treatment (13 patients). The treatment protocol consisted of oral isoprinosine (100 mg/kg/day), subcutaneous interferon alpha-2a (10 mU/m2/three times a week), and oral lamivudine (10 mg/kg/day). There were no statistical differences between the two groups according to Neurological Deficit Index, clinical stage, and average age on admission and also on the final evaluation after treatment. The mortality rates of both groups were similar: 3 (15.7%) for the treatment group and 6 (46%) for controls. The remission rates for the treatment and control groups were 7 of 19 (36.8%) and 0 of 13 (0%), respectively, and the difference was statistically significant (P = .036). The mean survival period of the treatment group was significantly longer than that of the control group (P = .01). In conclusion, this combination treatment protocol resulted in higher remission rates and longer survival periods when compared with controls, as well as a remission rate that was better than the spontaneous remission rate of 5%. For this reason, and as well as because interferon-alpha therapy has an easier route of application and a higher family compliance, we have considered this an alternative protocol for patients with subacute sclerosing panencephalitis.