Multiple pain-inhibitory systems dependent upon both opioid and nonopioid mechanisms of action have been identified, particularly in the rodent. The experimental subject has typically been the young, adult male rat, and generalizations concerning these systems have been made from this subject pool. This review focuses upon the roles of two organismic factors, aging and gender, in the modulation of analgesic processes. Using an array of age cohorts (4, 9, 14, 19, 24 months), these data illustrate that aging produces differential decrements in the analgesic responses following morphine, different parameters of footshock, continuous cold-water swims (CCWS: a nonopioid stressor), intermittent cold-water swims (ICWS: an opioid stressor) and 2-deoxy-D-glucose (a mixed opioid/nonopioid stressor). In contrast, neither beta-endorphin nor food deprivation analgesia is affected by aging. This review identifies that CCWS and ICWS analgesia are sensitive to gender differences, gonadectomy differences and steroid replacement differences such that females display less analgesia than males, gonadectomy reduces both analgesic responses, and that testosterone is most effective in reinstating gonadectomy-induced analgesic deficits. These data are considered in terms of therapeutic implications for the organismic variables under study as well as for the conceptual and methodological modifications that must be made in studying intrinsic pain inhibition.