Extensive evidence has indicated that distinct neural systems specifically designed to inhibit sensitivity to painful stimuli exist. Recent advances suggest that the endorphins, enkephalins and the opiate receptor interact with a descending serotonergic bulbospinal system to mediate the analgesic responses to opiates and electrical stimulation. In assessing the evolutionary and behavioral significance of this pain-inhibitory system, several laboratories discovered that acute exposure to a wide variety of stressful events results in a transient analgesia. Chronic exposure to a number of these stressors results in adaptation of the analgesic response. The purpose of this review is to identify and characterize the mechanisms by which these stressors activate pain-inhibition. The relationship of stress-induced analgesia to each of the following is reviewed: (a) the role of endorphins, enkephalins and the opiate receptor; (b) the role of the descending serotonergic bulbospinal system; (c) the role of the pituitary gland; and (d) the role of hypothalamic mechanisms. Data will be discussed in terms of "opiate" and "non-opiate" pain-inhibitory mechanisms, in which some stressors act through the former and other stressors act through the latter.