Cell surface components which are candidates for a role in nerve-target interactions specific for neurons of particular transmitter types in the sympathetic nervous system have been identified. Neurons of superior cervical ganglia of neonatal rats were dissociated and cultured in the virtual absence of non-neuronal cells under conditions previously found to control their choice of neurotransmitter. When raised in medium conditioned by heart cells, the neurons become cholinergic; when raised in medium which depolarizes them, the neurons remain in their original adrenergic state. The cell surface proteins of the neurons were labeled by either metabolic or surface-specific methods, separated by two-dimensional polyacrylamide gel electrophoresis, and visualized by autoradiography. A total of approximately 35 glycoproteins can be resolved, of which at least 14 are exposed on the cell surface. We evaluated glycoproteins of neurons raised under conditions which differ in their potency for inducing cholinergic properties: medium conditioned by skeletal muscle, liver, or heart cells or medium containing 1 mM butyric acid. The expression of three neuronal glycoproteins was correlated with the ability of a given culture condition to induce the synthesis and accumulation of acetylcholine or catecholamines. Two of these proteins are exposed on the cell surface, and the third appears to be identical with a protein previously shown to be secreted into the culture medium.