The evidence for stress activation of endorphinergic systems suggests a physiological role in endogenous analgesic and anti-anxiety regulation which would provide a reserve in emergency situations. The possibility of involvement of these systems in psychiatric illness arises from the psychotogenic and anxiolytic properties of some opiates. The endorphin-excess and -deficiency hypotheses of schizophrenia are reviewed in the light of naloxone's small but statistically significant antipsychotic action, and the activation of endorphinergic systems in the course of neuroleptic therapy. The hypothesis that endorphinergic deficiency may be present in endogenous depression is reviewed. Although alterations in beta-endorphin immunoreactivity measured peripherally and in CNS have not been substantiated, therapeutic trials using a mu-receptor agonist have shown promise of a rapidly-acting antidepressant effect. ECT is accompanied by increases in plasma beta-endorphin immunoreactivity.