Ten healthy male subjects were treated for three weeks with (+)oxaprotiline, a selective inhibitor of noradrenaline (NA) uptake and with (-)oxaprotiline which does not inhibit NA uptake. Plasma melatonin concentrations were measured throughout the night at 0, 1, 7 and 21 days and were higher during treatment with (+)oxaprotiline than with (-)oxaprotiline for the entire three weeks of treatment. Since NA stimulates the production and secretion of melatonin, these results are consistent with a sustained increase in noradrenergic activity within the pineal, during 21 days of treatment with an effective NA uptake inhibitor.