Morphine withdrawal behavior, brain and plasma catecholamine metabolites, and brain beta-noradrenergic receptor binding were examined after acute treatment with naloxone in rats treated with morphine pellets or a sham pelleting procedure. Increases in brain 3-methoxy-4-hydroxyphenethyleneglycol (MHPG), a norepinephrine metabolite, occurred in parallel with rated withdrawal behavior. Withdrawal behavior correlated significantly with brain, and, more modestly, with plasma levels of MHPG but did not correlate with beta-receptor binding or HVA. The effectiveness of debrisoquin sulfate was variable, but the reductions in withdrawal signs and cerebral cortex MHPG were strongly correlated. These data support a direct relationship between presynaptic noradrenergic hyperactivity and opiate withdrawal behavior.