Subjects with Down's syndrome have several immunological abnormalities. We examined the sera of 29 subjects with Down's syndrome for the presence of Fc gamma receptor blocking and for the presence of anti-ssDNA antibodies by EA rosette inhibition. Fifty-five percent of Down subjects had levels of inhibition above the upper limit of normality in comparison to 7% of normal controls. The finding that after polyethylene glycol precipitation of selected sera giving high levels of EA rosette inhibition there was a reduction or a disappearance of the EA rosette inhibition could indicate that the blocking factors detected behaved as immune complexes. Since almost all subjects with anti-ssDNA antibodies also had elevated values of EA rosette inhibition, a role for immune complexes eventually formed with autoantibodies in an Fc-mediated immunoregulatory system is suggested.