PHYSIOLOGICAL EFFECTS OF METHADONE ARE DESCRIBED ACCORDING TO ACUTE AND CHRONIC EFFECTS AND SHORT-ACTING AND LONG-ACTING NARCOTIC EFFECTS. ACUTE EFFECTS OF MORPHINE, FOR EXAMPLE, INCLUDE ANALGESIA, SOMNOLENCE, AND MOOD CHANGES. RESPIRATORY DEPRESSION OCCURS DUE TO DECREASE IN RESPONSIVENESS OF BRAIN-STEM RESPIRATORY. CENTERS AND RESULTS IN DECREASED RESPIRATORY RATE, MINUTE VOLUME, AND TIDAL EXCHANGE. HEROIN INJECTION CAUSES PHYSICAL DEPENDENCE, EUPHORIA, AND WITHDRAWAL SYMPTOMS DURING CHRONIC USAGE. METHADONE HAS NO OBVIOUS EFFECTS BUT CAN BE DETECTED AND MEASURED IN PERIPHERAL PLASMA OF PATIENTS IN MAINTENANCE PROGRAMS AND HAS ALSO BEEN MEASURED IN URINE, SWEAT, AND SOME OTHER BODY FLUIDS. THE MOST COMMON MEDICAL COMPLICATIONS OBSERVED IN PATIENTS RECEIVING METHADONE MAINTENANCE ARE PRIMARLY RELATED TO PREEXISTING CHRONIC DISEASES ACQUIRED DURING THE YEARS OF STREET USE OF NARCOTICS AND OTHER DRUGS; TO A WIDE VARIETY OF CLINICAL PROBLEMS WHICH ARE THE SAME AS THOSE IN THE GENERAL POPULATION OF PATIENTS WITH SIMILAR SOCIAL, ECONOMIC, AND LIVING CIRCUMSTANCES; OR TO PROBLEMS RELATED TO POLYDRUG OR ALCOHOL ABUSE. MOST FREQUENTLY THESE DISEASES INCLUDE LIVER, CHRONIC RENAL, AND VENEREAL DISEASE AND TUBERCULOSIS. SIDE EFFECTS NOTICED IN CHRONIC METHADONE MAINTENANCE PATIENTS ARE CONSTIPATION, EXCESSIVE SWEATING, AND INSOMNIA. PHYSIOLOGICAL AND BIOCHEMICAL SIDE EFFECTS ARE INDIRECT EVIDENCE OF RELEASE OF ANTIDIURETIC HORMONES, ABNORMAL METAPIRONE TESTS OF HYPOTHALAMIC RESEARCH, ABNORMAL PLASMA CORTICAL RESPONSE TO STRESS, ALVEOLAR HYPOVENTILATION, AND OTHERS. NO NEUROLOGICAL OR INTELLECTUAL FUNCTIONING ABNORMALITIES HAVE BEEN DEMONSTRATED. MANY POSSIBILITIES EXIST FOR FUTURE RESEARCH ON EFFECTS OF METHADONE, PARTICULARLY STUDIES TO CORRELATE EXOGENOUS NARCOTIC DISPOSITIONS, ENDOGENOUS ENDORPHIN-RECEPTOR INTERACTIONS, AND FEEDBACK MECHANISMS WITH OBSERVED PHYSIOLOGICAL EFFECTS AND THE PHENOMENON OF THE DEVELOPMENT AND MAINTENANCE OF TOLERANCE AND DEPENDENCE. TABULAR DATA AND REFERENCES ARE PROVIDED. FOR RELATED ARTICLES, PLEASE SEE NCJ 57805-57810 AND 57812-57834. (DAG)