The immunological reactivity to the stimulation with blood group substances was studied in nine cases of scleroderma and in nine normal subjects. Determinations were performed of the specific response (isohemagglutinins), the production of autoantibodies, and the appearance of anticoagulant factors. The specific antibody response was similar in both groups, as were the preimmunization titers. While none of the normal controls had autoantibodies or anticoagulant factors, the number of patients having positive tests before and after stimulation was as follows: antithyroid antibodies, 3,4; antinuclear factors, 0,1; lupus erythematosus (LE) cells, 1,1; syphilis test, 0,0; rheumatoid factors, 1,4; and anticoagulant factors 0,2. These studies reveal that patients with scleroderma have only minor disturbances in their immunological system and suggest that immunological hyperreactivity might not play an important role in the pathogenesis of scleroderma. However, investigations with other antigens would be necessary to draw clear-cut conclusions.