We compared the proteins transported in the fast component of guinea pig hypoglossal motor neurons with those of guinea pig vagus (preganglionic parasympathetic) neurons. The fast component proteins of hypoglossal and vagus neurons were radioactively labeled by injecting 3H-amino acids into the hypoglossal and vagus motor nuclei. The radioactive fast component proteins obtained from each system were then compared with each other by SDS-polyacrylamide slab gel electrophoresis and fluorography. These analyses revealed at least twenty polypeptides which appear common to the fast component of each neuronal system. In addition, we identified one difference between the proteins comprising the fast component of these neuronal systems. A polypeptide, molecular weight 50,000 daltons, present in the fast component of vagus neurons was not detected in the fast component of hypoglossal motor neurons. These observations are discussed with regard to the similarities and differences between these neuronal systems.