1. We have defined the descending efferent projections of the midbrain periaqueductal gray (PAG) by injecting small amounts of [3H]leucine into the various regions of the squirrel monkey PAG. 2. Despite the fact that different regions of the PAG were injected in separate animals, the majority of the brain stem areas labeled remained constant. 3. The PAG exhibited a dense projection to the superior colliculus, the nucleus cuneiformis, and the locus ceruleus. Parts of the reticular formation (nucleus reticularis: pontis oralis, pontis caudalis, gigantocellularis, magnocellularis, and ventralis) received a projection from the PAG, as did the nucleus parabrachial pars lateralis, ambiguous, the nucleus raphe magnus, and raphe pallidus. 4. In contrast to the brain stem, the deep laminae of the nucleus caudalis and the deep laminae of the cervical spinal cord were labeled only after injections of the lateral aspect of the PAG. 5. The main route for the PAG leads to brain stem projections is through the lateral edge of the paramedian reticular formation. The great majority of the anterograde labeling was ipsilateral to the injection although a small contralateral projection was present. 6. These results indicate that the PAG projects to the brain stem and spinal cord in the monkey. Many of the brain stem areas that the PAG projects to are known to project to the spinal cord. These secondary spinal projections coupled with the direct PAG leads to spinal projection provide a wide variety of routes through which the PAG may influence spinal cord activity.