Sensory gating is frequently found to be disturbed in patients with schizophrenia. In addition, a disruption of the circadian rhythm together with a low nocturnal melatonin output is regularly found in these patients. Since there is some evidence that a brief period of sleep normalizes sensory gating in schizophrenia patients, it is conceivable that their disrupted melatonin level may contribute to the deficits in P50 suppression. In this initial study, the effects of acutely administered melatonin on sensory gating in healthy subjects were investigated. In a double-blind placebo-controlled crossover design, 21 healthy male volunteers were administered melatonin (4 mg) or placebo, after which they were tested in a P50 suppression paradigm. In the group as a whole, melatonin did not affect P50 suppression. However, melatonin increased the P50 ratio in the individuals with high baseline suppression. In contrast to what was expected, melatonin reduced P50 suppression, albeit only in those individuals with high baseline suppression. The current study does not support a beneficial effect of acute exposure to exogenous melatonin on sensory gating. Future research should focus on melatonin's ability to restore basic sleep rhythms and its subsequent effects on sensory gating, in both healthy volunteers and patients with schizophrenia.