Antibody directed against insulin carries idiotypic determinants that may induce an auto-anti-idiotype (anti-Id) antibody response. We describe a solid-phase enzyme immunoassay which allows specific detection of IgG anti-Id directed against anti-insulin antibodies. Among 36 patients with type 1 diabetes, IgG anti-idiotype was detected in 21 (58%). An inverse significant correlation was found between titers of anti-idiotype and anti-insulin antibodies. These findings suggest that anti-idiotype antibodies may function to regulate the immune response to insulin. Whatever the mechanism of action of the anti-idiotype antibodies, we detected by ELISA, the clinical consequences and the theoretical implications of this determination may be important.