Stereotaxic fluid microinjections of horseradish peroxidase (HRP) into the periaqueductal gray (PAG), coupled with cortical HRP gel placements in macaque and cebus monkeys, have provided substantive retrograde and orthograde evidence that the rostral dorsal convexity and rostral medial prefrontal cortex are the principal sources of cortical-PAG projections. The prefrontal cortex projects to the dorsolateral quadrant of the PAG, precisely the area shown to receive spinothalamic inputs in mammals, including monkey. The findings are discussed in terms of a possible affective role in central analgesic mechanisms.