Clinical analgesic assays and concurrent pharmacokinetic studies on established and new narcotic agonists, narcotic agonist-antagonists and selected other analgesic drugs will be carried out in patients with postoperative pain or chronic pain due to cancer. Among other drugs, parenterally and orally administered heroin will be evaluated in this manner to determine whether it has any singularly desirable attributes for the management of patients with intractable pain due to advanced cancer. Studies are designed to categorize test drugs as narcotic agonists, agonist-antagonist and non-narcotic analgesics on the basis of how these drugs substituted as analgesics in patients already receiving narcotics for the relief of pain. The relationships of plasma, saliva and cerebrospinal fluid drug concentrations to analgesia and other pharmacologic effects of narcotics such as miosis will also be investigated. Single dose and steady state pharmacokinetic parameters of narcotics such as methadone, morphine and meperidine will be determined and an assessment made of how these parameters are influenced by narcotic tolerance and hepatic or renal dysfunction. An attempt will be made to measure the levels of endorphins in the cerebrospinal fluids of patients with and without pain, and in patients who have been hypophysectomized. As they become available, natural and synthetic endorphins will be assayed for their analgesic potency and selectivity of effect after intravenous and intraventricular administration. Finally, this research will address itself to the problems of measuring pain and analgesia in the clinical setting and in ways of improving the efficiency of clinical analgesic assays.