The effect of morphine tolerance-dependence, protracted and naloxone-precipitated abstinence on the levels of beta-endorphin and methionine-enkephalin in discrete brain regions, spinal cord, pituitary gland and plasma was determined in the male Sprague-Dawley rats. Among the brain regions examined, the levels of beta-endorphin in descending order were: hypothalamus, amygdala, midbrain, hippocampus corpus striatum, pons and medulla and cortex. The levels of beta-endorphin in midbrain, hypothalamus, and pituitary of morphine tolerant-dependent rats were decreased significantly. During protracted withdrawal beta-endorphin levels were decreased in amygdala, spinal cord and pituitary. During naloxone-precipitated abstinence beta-endorphin levels were increased in corpus striatum, midbrain and cortex. In addition, in naloxone-precipitated abstinence beta-endorphin levels were decreased in pituitary gland and hippocampus but increased in plasma. The levels of methionine-enkephalin in brain regions in decreasing order were: corpus striatum, pons and medulla, amygdala, hypothalamus, midbrain, hippocampus and cortex. The levels of methionine-enkephalin in pons and medulla, amygdala, hippocampus and pituitary gland were decreased in morphine tolerant-dependent rats. During protracted abstinence from morphine, methionine-enkephalin levels in spinal cord, amygdala, pons and medulla, midbrain, cortex, corpus striatum and pituitary gland were decreased. The levels of methionine-enkephalin in hypothalamus and corpus striatum of naloxone-precipitated abstinent rats were increased but were decreased in amygdala and pituitary gland. These results suggest that during morphine tolerance-dependence and during protracted abstinence beta-endorphin and methionine-enkephalin levels in discrete brain regions and pituitary gland are decreased.(ABSTRACT TRUNCATED AT 250 WORDS)