 In several historical studies melatonin has been given to human volunteers with no reports of toxicity. Waldhauser gave 80mg melatonin hourly for 4h to healthy men with no ill effects other than drowsiness and in healthy women given 300mgd for 4 months there were no side effects. Adverse effects are rare at doses 1g, but can include drowsiness, headache, hypothermia, pruritis, abdominal cramps, and tachycardia. Oral bioavailability of low doses was estimated at 15 of the parent compound but this makes no allowance for the known bioactivity of metabolites. We propose to undertake a dose escalation study in healthy volunteers to assess the tolerability of the doses proposed and to measure levels of exogenous melatonin and the major metabolites. This will provide crucial information to inform a subsequent application for a clinical trial of melatonin in patients with sepsis. 