It was long believed that melatonin might counteract intracellular oxidative stress because it was shown to potentiate antioxidant endogenous defences, and to increase the activity of many antioxidant enzymes. However, it is now becoming evident that when radicals are measured within cells, melatonin increases, rather than decreasing, radical production. Herein we demonstrate a pro-oxidant effect of melatonin in U937 cells by showing an increase of intracellular oxidative species and a depletion of glutathione (GSH). The activity of glutathione peroxidase is not modified by melatonin treatment as it does occur in other experimental models.