Eighty patients with Parkinson’s disease participating in a drug trial of L-dopa were studied prospectively for the development of antierythrocyte, antinuclear, and antiglobulin activities. The median age of the group was 65 years; and the median dose of L-dopa was 4 g/day. Five of the 80 patients developed positive red cell antiglobulin tests after 8 to 11 months of therapy. Three of these had IgG only on their red cells ; eluates prepared from these cells reacted strongly with all except Rhnun erythrocytes, suggesting Rh specificity. Complement only was detected on the cells of the other 2 patients. One of the 5 individuals with positive erythrocyte antiglobulin tests became anemic. Significant titers of antinuclear antibody appeared in 9 patients and significant increases in titers of serum antiglobulins were found in 9 patients, 2 of whom also had a positive ANA test. These results indicate that administration of L-dopa is associated with induction of a variety of autoantibodies. The mechanism responsible for this phenomenon is unknown.