Since previous studies have shown that an active pineal gland exerts an inhibitory effect on circulating levels of thyroxin in the Syrian hamster, a study was conducted to determine whether the histology and ultrastructure of the thyroid gland supported the conclusions drawn from the hormone data. The ultrastructure of thyroid glands of blinded male Syrian hamsters was compared to that of intact controls kept under a 14L/10D photoperiod, to that of blinded hamsters also pinealectomized, and to that of blinded hamsters receiving 80 micrograms/ml of melatonin in the drinking water. Serum thyroxin (T4) and serum thyrotropin (TSH) concentrations were determined by radioimmunoassay. After 10 weeks serum thyroxin concentrations were less than 50% of controls and concentrations were significantly reduced. EM examination revealed that blinded hamsters had an increased number of follicular cells with flattened epithelium and nondilated endoplasmic reticulum compared to intact controls. In blinded hamsters that were pinealectomized or treated with melatonin in the drinking water, the ultrastructure of the thyroid was not different from controls and serum thyroxin concentrations were restored to near normal. These ultrastructural data support the conclusion that the pineal gland is required to obtain inhibition of the pituitary-thyroid axis in blinded hamsters and that melatonin has a counter-inhibitory effect when administered via the drinking water.