Melatonin's neuroprotective action has been demonstrated in experimental models of brain ischaemia. The relationship between stroke and melatonin levels has been based on scarce and small sample size studies. In addition, the changes have not been correlated with the age of patients. We compared levels of nocturnal urinary melatonin and its metabolite, 6-sulfatoxymelatonin (aMT6S) in a large series of acute ischaemic stroke patients and healthy volunteers. Consecutive ischaemic stroke patients with a first episode of anterior circulation stroke were recruited. Urine samples were collected in 127 patients on day 1 poststroke and in a control population including 216 healthy volunteers, from 20:00 to 08:00 hr. Melatonin and aMT6S were measured by radioimmunoassay. Differences in melatonin and aMT6S levels between ischaemic stroke patients and healthy volunteers were assessed by gender and age categories, using the Student's t-test. Melatonin excretion was decreased in stroke patients compared with healthy volunteers (74.1 +/- 13.9 versus 211.9 +/- 31.0 ng/hr; P = 0.0004), whereas aMT6S level was not significantly reduced (6371 +/- 1028 versus 4469 +/- 508 ng/hr; P = 0.10). Conversely, the stratification by age showed a significant reduction of both melatonin and aMT6S levels among ischaemic stroke patients over 70 yr (P = 0.001 and P = 0.03 respectively). The impact of melatonin at the acute stage of stroke on clinical severity and lesion size needs further assessment, as melatonin may have potential neuroprotective effects.