A 27-year-old man with psoriasis was administered with leukocyte derived interferon-alpha for the treatment of chronic persistent hepatitis C. After 3 weeks of injections and eventual normalization of serum levels of alanine aminotransferase, he began to experience polyarthritis, with worsening of psoriatic skin lesions. Tests for antinuclear antibodies and rheumatoid factor were negative, indicating a direct association between interferon therapy and occurrence of seronegative arthritis.