Twenty-nine patients, 27 of them with osteosarcoma and two with juvenile laryngeal papilloma, were followed for an aggregate period of 365 months, during which time they received long-term treatment with human leukocyte interferon. The interferon was given by intramuscular injection either daily or three times a week; the dose was 3 x 10(6) standard units. During the course of the treatment, 12 distinct symptoms were recognized as possible side effects of the drug; the three most frequent symptoms occurring after injection were fever, local pain, and shivering. All but three of the patients reported between one and five symptoms. Partial purification of the interferon reduced or eliminated some, but not all, of the symptoms. All of the patients were treated on an ambulatory basis, and none had to discontinue the interferon therapy because of the side effects.