The therapeutic use of interferon (IFN)-α administered as adjuvant medication in chronic schizophrenia was investigated. Natural leukocyte IFN-α was given to 9 long-term hospitalized chronic schizophrenic patients daily as subcutaneous injection of 3 million units 5 times a week. The trial followed a placebo-controlled double-blind crossover design. Each treatment period lasted for 8 weeks with a 2-week washout period in between. IFN-α did not prove to be beneficial for the total group of patients. Yet, 3 patients improved during the IFN-α drug period. The clinical improvement was seen as better social competence and less affective tension in the ward surroundings.