Two Japanese encephalitis cases with serious comatous symptoms were treated with the Human Recombinant Interferon-alpha A. The clinical responses to IFN were found to be satisfactory. The first case showed improvement on the 5th day of IFN treatment and the general condition slowly improved. The second case recovered from the comatous stage on the 6th day of IFN, followed by quick improvement of general symptoms in the 2nd week and complete recovery without any mental sequelae. Leukopenia and neutropenia occurred during the first week of administration of IFN, but were only temporary. Slight elevation of SGOT and SGPT was observed in the first case. No other side effects including general toxicity, neurotoxicity or allergy, or any abnormal hematological and blood chemistry changes were observed in these 2 cases. Two other JE cases (the 3rd and 4th consecutive JE cases) were not treated with IFN, but received the usual regimens of symptomatic and supportive drugs. Both patients died on the 7th-9th day of illness. This study suggests that the Human Recombinant Leukocyte A Interferon possibly is an effective and promising agent in the treatment of Japanese encephalitis in Thailand. More studies to treat JE cases with this IFN are being performed in order to assess the efficacy, tolerance and safety of rIFN-alpha A on Japanese encephalitis in Thailand.