Recent findings suggest that the periaqueductal gray (PAG) can be subdivided on the basis of its anatomical connections and functional representation of cardiovascular and behavioral functions. This new scheme of subdivision postulates the existence of 4 major longitudinal columns located dorsomedial, dorsolateral, lateral and ventrolateral to the aqueduct. Attention has focussed on the lateral and ventrolateral columns, because they contain topographically distinct groups of neurons whose activation results in different forms of defensive or protective reactions. Reactions evoked from the lateral PAG column are associated with somatomotor and autonomic activation and are characteristic of an organism's response to superficial or cutaneous noxious stimuli, whereas reactions evoked from the ventrolateral PAG column are associated with somatomotor and autonomic inhibition and appear to correspond to an organism's response to deep or visceral noxious stimuli. Furthermore, the neurons of these two columns possess some degree of somatotopic and viscerotopic organization and send axon collaterals to multiple targets in the medulla. This model of PAG neuronal organization outlines the basic architectural features of a network involved in the coordinated expression of certain types of defensive/protective reactions.