A common serologic finding in autoimmune diseases is the presence of autoantibodies against intracellular autoantigens. Recent data suggest that an anti-idiotypic network exists in these diseases, regulating the production of autoantibodies (idiotypic response). The anti-idiotypic antibodies can be monitored using complementary epitopes, designed according to the “molecular recognition” theory. The role of antiidiotypic antibodies in neonatal lupus and type 1 diabetes are discussed. In neonatal lupus, mothers with high anti-idiotypic antibody activity against anti-La autoantibodies are at lower risk of giving birth to an un-healthy child, as compared with mothers without anti-idiotypic antibodies. Similarly,the lack of particular anti-idiotypic antibodies against anti-GAD65 autoantibodies predispose in type 1 diabetes. These findings imply that antiidiotypic antibodies may confer protection from the harmful effect of autoantibodies in certain autoimmune diseases [corrected].