The effects of altered thyroid function on the levels of histamine, histidine decarboxylase activity and the number of mast cells were studied in the brain of 5-day-old rats. At this age both brain histamine levels and mast cells number are at a maximum. In addition the major portion of the amine is stored in mast cells and upon subcellular fractionation it sediments in the crude nuclear fraction (P1). Treatments with thyroid hormones or thyrotropic hormone up to 5 days of age leads to a decrease in the histamine levels and mast cells number in the brain, whereas administration of the antithyroid agent 6-n-propyl-2-thiouracil increases both parameters. All treatments affected only the histamine in the P1 fraction and failed to alter the levels of neuronal histamine which is located in the supernatant of P1 (S1). These facts suggest that in neonatal rat thyroid hormones could be involved in the regulation of the levels of brain histamine by regulating the number of brain mast cells.