Previous work in this laboratory established that selective attention, as measured by the behavioral and autonomic expressions of the orienting response (OR), is not disrupted by either dopaminergic or cholinergic receptor blockade. The present experiments extended this pharmacological analysis of the OR. In Experiment 1, preweanling rats were injected with methysergide maleate, a serotonin receptor blocker. Neither the behavioral nor the heart rate (HR) component of the OR was attenuated. In Experiment 2, the opiate receptor blocker naltrexone also failed to inhibit the HR and behavioral expressions of the OR. alpha-1 adrenergic receptor blockade with WB-4101 in Experiment 3 abolished both the HR and behavioral ORs to the pulsating tone. In Experiment 4, clonidine, which inhibits release of norepinephrine by stimulating alpha-2 autoreceptors, attenuated both behavioral and HR ORs to the pulsating tone in a dose-dependent manner. These data, in combination with the prior findings, suggest that norepinephrine is critically involved in the central process underlying the OR in the rat. Dopaminergic, cholinergic, serotonergic, and opiate receptor blockades do not impair selective attention as indexed by HR and behavioral ORs to an auditory stimulus. In contrast, disruption of noradrenergic functioning via either alpha-1 receptor blockade or alpha-2 receptor stimulation disrupts both the HR and behavioral components of the OR. These results indicate that integrity of central noradrenergic functioning is essential for expression of the OR and for stimulus-directed attention.