Maternal humoral immune responses against antigens of the genetically alien embryo have been reported in several mammalian species, including man, although little is known of the biological relevance of this phenomenon. In the mouse, only females of certain inbred strains mated repeatedly with an allogeneic male produce antibody directed against paternally inherited fetal histocompatibility antigens, as assessed by haemagglutination techniques^1–4. It has been suggested that this characteristic of the female is associated with the H–2^b haplotype³, although some reports indicate that it also extends to other H–2 types⁵. Potentially deleterious complement-dependent cytotoxicity, albeit at low levels, has been claimed to be associated with this alloantibody, but we have been unable to detect any such activity in a large number of maternal sera⁶. Four IgG isotypes (IgG1, IgG2a, IgG2b and IgG3) have been identified and shown to occur in the serum of normal animals^7,8. Despite their similar physicochemical properties, which complicate purification procedures, the availability of immunoglobulin-secreting plasmacytomas has made possible the preparation of isotype-specific antisera^9,10. Using these antisera in a modified haemadsorption assay¹¹, we have now demonstrated that the major alloantibody response induced by murine pregnancy involves the non-complement-fixing IgG1 subclass. This is a noncytotoxic antibody with potentially protective (enhancing) properties¹².