IgG4 anti-IgG autoantibodies were found to be present in all serum samples from a group of healthy people; IgG4 ant-IgA and anti-IgE were present In only 13 of 218 (6%) and 8 of 218 (3.5%) samples, respectively. These antibodies also showed affinities towards animal immunoglobulins. We suggest that IgG4 anti-IgA antibodies (the strongest found heterophilic Immunoglobulins) are responsible for most artifacts obtained with commercial EUSA systems.