Hyperactivity of noradrenergic locus coeruleus (LC) neurons following withdrawal from chronic opiates has been implicated in the opiate withdrawal syndrome. Here, we report that local withdrawal induced in vivo by microinfusion of an opiate antagonist into the LC of morphine-dependent rats marginally, but significantly, activated LC neurons above the level obtained with local naloxone microinfusion in naive rats. This local withdrawal response contributes a significant fraction (approximately 19%) of the total LC hyperactivity induced by systemic naloxone.