L-Dihydroxyphenylalanine (L-DOPA)significantly inhibited intrathyroidal colloid droplet formation induced by exposure to cold in the rat. Diethyldithiocarbamate (DDC) also inhibited colloid droplet formation in response to cold. The combined administration of L-DOPA and DDC produced an additive inhibition of the thyroidal endocytotic response to exposure to cold. Pretreatment with chlorpromazine (CPZ) ameliorated the inhibitory effect of (L-DOPA)DL-alpha-methyl-p-tyrosine (α-MT) also significantly depressed the thyroidal response. Inhibition of colloid droplet formation induced by α-MT was not altered by the administration of DL-dihydroxyphenylserine (DL-DOPS). On the other hand, treatment of the α-MT-treated rats with L-DOPA to normalize dopamine synthesis resulted in a dramatic recovery from the inhibition. Blockade of serotonin biosynthesis with p-chlorophenylalanine (p-CPA) failed to produce a significant inhibition of colloid droplet formation. However, 5-hydroxytryptophan (5-HTP) markedly inhibited the thyroidal response to cold. Brocresine phosphate (BP) was another inhibitor of the thyroidal endocytotic response to exposure to cold. Oxotremorine also markedly depressed the thyroidal response to cold. Since these drugs did not interfere with pituitary-thyroid responsiveness to exogenous thyrotropin-releasing hormone (TRH), it seems that the thyroidal endocytotic response to exposure to cold as a reflection of TSH secretion was directly influenced by alterations of brain biogenic amine concentrations or turnover rates.