Using a panel of self antigens, IgM autoreactivities were clearly and constantly detected by enzyme immunoassay (EIA) in the sera of 29 normal human individuals. Similarly, IgM autoreactivities in sera were reproducibly detected by immunoblotting, using human organ extracts as the antigen sources. In contrast, IgG reactivities were low in whole sera but were considerably increased after affinity-chromatography purification on protein G-Sepharose. These increases differed from one individual IgG preparation to another and from one antigen to another (from 1-94 times) resulting in a unique IgG autoreactivity pattern for each subject. IgG reactivities diminished markedly when the IgG-depleted serum was added to the isolated autologous IgG. IgM antibodies isolated from sera on F(ab')2 IgG immunoadsorbent partially inhibited the binding of IgG to tubulin and myosin but not to actin. The individual IgG preparations examined separately exhibited, with all the autoantigens of the panel, higher autoreactivities than those of the same-but-pooled IgGs, which in turn were higher than those of a commercially available human IgG preparation obtained from approximately 8,000 healthy donors and used for intravenous injection. Depending upon the individual IgG sample, 31-65% of the IgG were bound to a DNP-Sepharose column and were eluted with DNP-glycine. The isolated anti-DNP antibodies were found to be polyreactive and possess higher autoreactivities than the original IgG preparation for all the antigens of the panel. Similarly, IgG antibodies analysed using an antibody exchange procedure were found to be essentially polyreactive but some apparently monospecific antibodies were also noted. These results suggest that the great majority of IgG present in normal humans are composed of polyreactive autoantibodies. IgG autoreactivities are only marginally expressed in these whole sera because of IgM-IgG, IgG-IgG and other, still unidentified, interactions.