Toward identifying molecules involved in cell-cell interactions during cerebral cortical development, we have investigated the nature of immunoglobulin-like immunoreactivity (Ig-ir) in the murine cortex. Immunohistochemistry using several antisera recognizing IgG revealed intense immunoreactivity in the subplate and marginal zone of embryonic day 16 cortex, as well as in the hindbrain and spinal cord, particularly within ventral fiber tracts. In three independently derived mouse strains lacking the recombination activating genes RAG-1 or RAG-2, which are essential for Ig production, Ig-ir was absent from the fetal CNS. Western blot analyses of wild-type brains from embryonic day 12 through birth identified a 25 kDa protein that co-migrated with Ig light chain and was absent from RAG-1 or RAG-2 -/- brain samples. This result could be replicated with an antiserum specific for Ig kappa light chain, but not with antisera specific for Ig gamma or mu heavy chain. No Ig-ir was detected in the brains of RAG-1 +/- embryos carried by a -/- female, suggesting a maternal source of the immunoreactive molecule. In confirmation of this, Ig-ir could be partially reproduced by intraperitoneal injection of pregnant RAG-1 -/- females with normal mouse serum. We conclude that maternally derived Ig light chain is present in the fetal murine CNS. This may represent a novel maternal contribution to fetal neural development and implicates Ig molecules as potential mediators of cortical developmental events.