Thirteen months after starting methyldopa therapy, a 55-year-old white male patient presented with a syndrome of hemolytic anemia, arthritis, photosensitivity, and a positive antinuclear antibody test result. Methyldopa-induced antinuclear antibodies were mainly IgG, directed against class H1 histones. Antibodies to native DNA and nonhistone proteins were not detected. Upon withdrawal of methyldopa therapy, and with a short course of prednisone and danazol therapy, the patient's symptoms and hemolytic anemia resolved. His clinical symptoms and serologic abnormalities returned to normal and remained negative after 2 years of followup.