Sera from U.S. patients with SLE, RA, and various malignancies, clinically normal individuals with seroactivity to HIV, AIDS, and from pregnant women were tested for the presence of anti-c-mycantibodies. In an ELISA using recombinant humanc-mycprotein as the antigen, no difference in mean antibody liter was generally detected in these sera when compared to normal controls. Only three malignancy sera (two myeloid leukemia and only one lymphoma) and two patients with AIDS-related lymphoma exhibited exceedingly higher levels of anti-c-mycantibody. However, significantly elevated anti-c-mycantibody levels were found among 20 patients with African Burkitt's lymphoma (Ghana) and 20 normal Ghanians, thus apparently reflecting an autoimmune phenomenon prevalent in the endemic region. These findings indicated that elevated levels of anti-c-mycantibodies are not a general characteristic of patients with diseases that have been associated with increased expression ofc-myc.