The effects of morphine tolerance-dependence and abstinence on 5-HT2 receptors in brain and spinal cord of the rat were determined. Tolerance to and physical dependence on morphine was induced in male Sprague-Dawley rats by implanting six morphine pellets (each containing 75 mg of morphine free base) during a seven day period. Two groups of rats were used for binding studies. In one group the pellets were left intact and in the other they were removed. The rats were killed and spinal cords and brains were excised and dissected into six regions (amygdala, hippocampus, hypothalamus, striatum, midbrain and pons + medulla). 5-HT2 receptors were characterized by using [3H]spiperone as the ligand and unlabelled ketanserin to determine the non-specific binding. In morphine and placebo abstinent rats the binding of [3H]spiperone to 5-HT2 receptors in brain regions and spinal cord did not differ. The Bmax values of [3H]spiperone to bind to membranes prepared from non-abstinent morphine-dependent rats were increased in amygdala (78.0%), midbrain (65.0%) and pons + medulla (92.0%). The Kd values were unaffected. It is concluded that in morphine-tolerant-dependent rats 5-HT2 receptors are up-regulated in amygdala, midbrain and pons + medulla, but in morphine-abstinent rats they are unaffected.