The expression of the polysialic acid neural cell adhesion molecule (PSA-NCAM) in the hypothalamo-neurohypophyseal system has been correlated with morphofunctional plasticity. In this study, we investigated the role of PSA-NCAM in the survival of oxytocin (OT)- and vasopressin (VP)-producing magnocellular cells of this system. We used a recently developed organotypic slice culture model of the rat hypothalamic paraventricular nucleus (PVN) in which ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) are potent survival factors for magnocellular neurons. We demonstrate by means of confocal microscopy that cultured magnocellular VP and OT neurons express strong immunoreactivity for PSA-NCAM. Removal of PSA from NCAM by the enzyme Endo N leads to a significant loss of both VP and OT neurons in the presence of low concentrations of CNTF. Endo N treatment did not change cell survival in the presence of LIF. These results suggest that, in addition to its role in neuro-glial plasticity, PSA-NCAM might also influence the trophic factor responsiveness of hypothalamic VP and OT neurosecretory cells.