Previous work has shown that the activity of the melatonin-forming enzyme in the rat pineal gland is elevated in rats kept in continuous darkness as compared to those kept in continuous light. Information about environmental lighting reaches the pineal gland via nerves that liberate noradrenaline. Rat pineal glands in organ culture can form C(14)-melatonin from C(14)-tryptophan as follows: tryptophan --> 5-hydroxytryptophan --> serotonin --> melatonin. Noradrenaline was found to stimulate the synthesis of C(14)-melatonin from C(14)-tryptophan in rat pineals in organ culture. Other compounds related in structure to noradrenaline increase melatonin and serotonin synthesis and inhibit the formation of the deaminated product of serotonin, 5-hydroxyindole acetic acid. Cycloheximide, a compound that inhibits protein synthesis, also prevents the formation of serotonin, melatonin, and 5-hydroxyindole acetic acid from tryptophan in pineal organ culture. These observations suggest that noradrenaline liberated from sympathetic nerves stimulates the formation of melatonin either by increasing the formation of new melatonin-forming enzyme, by increasing transport of tryptophan into the pineal cell, or by inhibiting the metabolism of serotonin by the alternate deaminating pathway.