The subcommissural organ (SCO), which belongs to the circumventricular organs, is a specialized ependymal structure of the brain that secretes glycoproteins into the cerebrospinal fluid (CSF) which condense to form a thread-like structure; Reissner's fiber (RF). The effects of soluble material released by RF were examined in primary cultures of dissociated cortical cells from embryonic (day 8) chick brain. Under serum-ii ee conditions, the presence in the cultures of soluble RF material markedly impaired neuronal cell aggregation. This effect was completely blocked by addition into the culture medium of specific antibodies raised against bovine RF. The anti-aggregative effect of soluble RF material is observed on poly-L-lysine as well as on different extracellular matrix proteins including collagen and laminin, but was less effective an fibronectin. The continuous exposure of the cultures to soluble RF material for 7 days significantly decreased choline acetyltransferase activity. On the other hand, soluble RF material did not appear to have mitogenic activity on neuronal cultures, Modulation of cell-cell interactions by SCO/RF glycoproteins strengthens the hypothesis of the involvement of RF in developmental events of the central nervous system.