An intense but task-irrelevant auditory accessory stimulus that is presented almost simultaneously with a visual imperative stimulus can reduce reaction times (RTs) to that stimulus. The information-processing locus and neural underpinnings underlying this phasic alerting effect are still poorly understood. The authors investigated a possible noradrenergic or cholinergic basis of the accessory stimulus effect in a double-blind pharmacological study (N = 18), in which healthy participants received a single dose of clonidine (an α2-adrenergic agonist), scopolamine (a muscarinic antagonist), and placebo in separate test sessions. A backward-masking procedure was used to examine, for the first time, the effect of accessory stimuli on perceptual sensitivity. The authors found that accessory stimuli enhanced perceptual sensitivity and decreased RTs to target stimuli, consistent with a recent hypothesis that phasic alerting speeds up stimulus encoding. In contrast to the authors' expectations, clonidine increased the accessory stimulus effect, a finding that seems at odds with earlier proposals that phasic alerting effects are mediated by a phasic noradrenergic response. Furthermore, the accessory stimulus effect was modulated to a similar extent by clonidine and scopolamine, suggesting that the effect of clonidine was not specific to the noradrenergic system. The results instead suggest that clonidine and scopolamine decrease general alertness and that these drug-related reductions in alertness yield room for compensatory performance improvements by phasic alerting.