Changes in central neurotransmission and in hypothalamo-pituitary function occur in both ethanol (ETOH) intake and withdrawal. Melatonin (MLT) secretion is regulated by the noradrenergic system, which is activated upon ETOH withdrawal. Experimental evidence exist that pineal gland may have a role in ETOH intake and preference in rats. Twenty-four hour urinary excretion of MLT was found to be increased during ETOH intake in chronic alcoholics. In this study we have determined 24h plasma levels of MLT and cortisol in 8 chronic alcoholic males hospitalized for a detoxication program and in 8 healthy controls. The study was performed just after admission, on the first day of ETOH withdrawal and after 14 days of controlled abstinence. Circadian periodicity has been evaluated by the cosinor method. The initial determinations corresponded to the acute withdrawal phase. Twenty-four hour plasma MLT mean levels on acute withdrawal were higher than after 14 days abstinence and than those found in controls. Large interindividual differences prevented the detection of statistical significance. The cosinor analysis disclosed the loss of circadian periodicity in the acute withdrawal. Significant 24h periodicity was restored after 14 days abstinence. Cortisol levels were significantly higher than those found on day 14 and in healthy controls. Twenty-four hour periodicity was maintained in both alcoholics series. A delay in cortisol acrophase occurred in acute withdrawal. The effects of Corticotropin Releasing Hormone infusion on cortisol secretion were significantly enhanced in the acute withdrawal phase in comparison with those occurring when patients were retested and with healthy controls.