Detection of salient or motivationally significant stimuli is of adaptive importance. The neurophysiological correlates of this detection have been extensively studied in 'oddball' paradigms. Much theoretical data supports the role of noradrenergic systems in generating oddball responses. We combine psychopharmacology and functional neuroimaging to demonstrate modulation of neuronal responses to oddball nouns by the beta-adrenergic antagonist propranolol. Critically, responses in regions implicated in oddball detection, namely right ventrolateral prefrontal cortex and temporoparietal junction (TPJ), were abolished by propranolol. Thus, oddball responses depend on modulatory adrenergic inputs, mediated via beta-adrenergic receptors.