The evoked response to repeated auditory stimuli generally decreases in amplitude, a phenomenon that demonstrates the activity of sensory gating mechanisms in the central nervous system (CNS). Gating of the P50 wave of the auditory evoked response shows such behavior in normals, but not in schizophrenic or manic subjects. In mania, diminished gating of the auditory evoked response is correlated with elevated levels of noradrenergic metabolites. In animals, yohimbine, a presynaptic alpha-2 antagonist, increases noradrenergic neuronal transmission in the CNS and diminished gating of the auditory evoked response. The aim of this experiment was to test whether yohimbine causes diminished auditory sensory gating in normal human controls. Seven normal subjects with normal P50 auditory gating were treated either with 0.4 mg/kg of oral yohimbine on one day or placebo on a different day. Each subject acted as his own control. Yohimbine, but not placebo, caused a significant but transient decrease in P50 auditory gating in these subjects. Thus, increasing CNS noradrenergic neuronal transmission in normal controls can cause a transient impairment in auditory sensory gating.