Anti-BPM is a neuron-specific antiserum which specifically recognizes the D2 cell adhesion molecule in crossed immunoelectrophoresis of Triton X-100-solubilized brain extracts. Here the effect of this antiserum on the in vitro development of cerebellar neuronal cultures is described. The initial adhesion of cells and neurite outgrowth were not influenced by immunoglobulin fractions of anti-BPM. However, after 5 days in vitro the cultures had become completely disorganized, with the majority of cells being dead at immunoglobulin concentrations greater than 0.5 mg/ml culture medium. This effect was seen only with immunoglobulins and their F(ab')2 fragments, the F(ab') fragments being without effect. The addition of anti-BPM to 8-day-old cultures resulted in a more rapid and pronounced rate of cell death. In many instances this was preceded by a rapid "destabilization" of culture organization. The cytotoxic effect of anti-BPM was neuron specific and the small numbers of astrocytes and fibroblasts found in the cultures were unaffected by prolonged exposure to this serum.