The appearance and developmental distribution of GD3 and polysialogangliosides was studied immunohistochemically by means of the monoclonal mouse antibodies AbR24 and Q211. Cryostat sections of chicken embryos from 1 to 5 days (E1-E5) of incubation (Hamburger and Hamilton, stages 9-26) were prepared. GD3, detected by AbR24, is expressed on E2 by proliferating neuroepithelial cells of all regions of the developing brain and spinal cord and by migrating neural crest cells. As development continues, GD3 drops to a much lower level in postmitotic neurons, but is still strongly expressed by cells of the mitotically active germinal zones. In non-neural tissues the antigen was found in much lower concentrations than in the neuroectoderm, with the exception of very early, heavily proliferating endodermal and mesodermal epithelia. In contrast, the antigen(s) of the monoclonal mouse antibody Q211, identified on TLC-plates in polysialoganglioside fractions, was found to be specific for central and peripheral derivatives of the neural ectoderm. In the CNS, these polysialogangliosides are absent in the proliferating neural epithelium and appear for the first time on cells of the developing peripheral mantle layers at E2.5 (stage 17). Sections from all brain areas, retina, optic stalk, spinal cord, and peripheral nerves and ganglia of later stages (E4-5) showed that the antigen(s) of Q211 is expressed by neuronal perikarya and cell processes. The data strongly suggest that the developmental appearance of these polysialogangliosides is synchronized with the withdrawal of proliferating precursor cells from the mitotic cycle and differentiation to neurons.