Human leukocyte interferon was administered systematically to 13 Japanese patients and its side effects were evaluated. Systemic administration of interferon caused a temporary febrile response in most of the patients. Intravenous injection caused a more severe but shorter response than intramuscular injection. The long-term administration of interferon caused an increase in neutrophils for one or a few months in six patients. No other side effects were found in any of the patients. Because the side effects may be due to the impurity of the interferon preparations, more highly purified interferon should be used from now on.