The isotype distribution of human IgG antibodies reactive with common dietary proteins has been evaluated in sera from adult patients with the irritable bowel syndrome and with bronchial asthma using a solid-phase immunoassay (ELISA). In both these medical disorders, serum antibodies reactive with ovalbumin or gliadin were restricted predominantly to the IgG4 isotype; however, IgG antibodies reactive with bovine milk antigens, notably casein, were often restricted to both the IgG2 and IgG4 isotypes. A similar serum IgG antibody isotype distribution for these dietary protein antigens was also demonstrated in IgG antibody-positive healthy adults. These data amplify the view that production of antibodies of the IgG4 isotype may reflect a normal immune response to dietary protein antigens presented at mucosal surfaces.