The effects of the α-agonists clonidine and guanfacine on rat cortical norepinephrine turnover during morphine withdrawal were assessed. Cortical norepinephrine levels were measured, after administration of α-methyl-p-tyrosine, by fluorometric assay. Chronic treatment with morphine did not affect norepinephrine levels or norepinephrine turnover. In control animals, doses up to 200 μg/kg clonidine and 1060 μg/kg guanfacine did not affect norepinephrine steady state levels, but did reduce α-methyl-p-tyrosine-induced norepinephrine depletion. As little as 5 μg/kg clonidine reversed the accelerated turnover observed during naloxone precipitated morphine withdrawal; while for guanfacine, the minimum effective dose was 212 μg/kg. The ED 50 for guanfacine's reversal of the withdrawal-induced acceleration of turnover was approximately 60 times that for clonidine.