Pineal melatonin secretion exhibits a rhythm which is identified as a circadian cycle with a period of between 20 and 28 h in most animals. The melatonin rhythm has an acrophase of about -30 degrees. The aim of this study was determine the effect of lithium on the melatonin rhythm since lithium is usually used as a therapeutic agent in manic-depressive desease. Lithium induced a delay of the melatonin acrophase which reached a value of about -45 degrees; lithium also produced another peak which had an acrophase at about +60 degrees. We speculate that lithium influences either inositol phosphate turnover or it merely changes the profile of the melatonin rhythm.