Electrical stimulation of the central nucleus locus coeruleus (LC) was previously shown to increase activity of the peripheral sympathetic nervous system (SNS) as measured by increases in plasma levels of the norepinephrine (NE) metabolite 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) in the rat. Four experimental approaches were designed to test the specificity of the LC cell group in activating the SNS in the stimulation paradigm. Varying the stimulation current amplitude, varying the site of stimulating electrode placement, and electrolytic lesions of the LC yielded results consistent with the hypothesis that the site of SNS activation was within the anatomical region of the LC cell group. Neurochemical lesioning with intraventricular 6-hydroxydopamine, however, did not effectively block the plasma MHPG increase observed after stimulation of the LC region. The possibility that non-noradrenergic cells, fibers of passage, or terminals in the LC region of the midbrain may be responsible for SNS activation when the LC is electrically stimulated is discussed. These studies are pertinent to all studies of LC function which employ electrical stimulation of the LC nucleus, including investigations of the role of the LC in social behavior, intracranial self-stimulation, and blood pressure regulation.