In vertebrates, almost all motor neurons innervating skeletal muscles are located in the hindbrain and spinal cord, and all brain centers that control behavior have descending projections into these parts of the central nervous system. With tracer injections into the spinal cord and hindbrain, we have studied cell groups with descending projections in the paddlefish. Spinal cord injections reveal retrogradely labeled cells in all reticular and raphe nuclei, as well as the nucleus of the medial longitudinal fascicle. Additional cell groups with projections to the spinal cord are the nucleus of the fasciculus solitarius, descending trigeminal nucleus, several octavolateral nuclei, the dorsal hypothalamic nucleus, and the pretectum. The only primary sensory fibers with descending projections are trigeminal fibers. Hindbrain injections reveal a number of additional cell groups in di- and mesencephalon. The most prominent source is the mesencephalic tectum. Other descending cells were found in the dorsal posterior thalamic nucleus, ventral thalamus, torus semicircularis, lateral mesencephalic nucleus, and the central gray of the mesencephalon. Our data show that descending spinal projections are comparable to those of other vertebrates and that the tectum is the most important motor control center projecting to the hindbrain. A surprising result was that the dorsal posterior thalamic nucleus also projects to the hindbrain. This nucleus is thought to be a center that relays sensory information to the telencephalon. Further studies are needed to determine the complete set of projections of the dorsal thalamus in paddlefish and other fishes to gain insights into its functional role.