To examine the relationship between the functioning of the adrenal and thyroid glands in sheep, plasma cortisol concentration, concentration of protein-bound 125I from thyroid vein plasma, heart rate and blood pressure were measured in ewes bearing exteriorized thyroid glands. During these measurements stresses were imposed on the animals: fear induced by pistol shots or by a barking dog, cold by cooling and wetting, and physical restraint by a loose harness. Increases in plasma cortisol concentration of 2-6 mug/100 ml were observed with each type of stressor, the response rapidly decreasing with habituation of the animal. Increases in the concentration of protein-bound 125I from thyroid vein plasma were also observed repeatedly during cooling and wetting, occasionally after the introduction of a barking dog, and during continued restraint. Cooling and wetting was the only stress causing consistent parallel activation of the adrenal cortex and thyroid gland; the other stressors resulted in independent fluctuations of secretions, as indicated by plasma cortisol concentration and concentration of protein-bound 125I from thyroid vein plasma. No reciprocal relationship between thyroid gland and adrenal cortex activity was detected. It was concluded taht these ewes, which had been accustomed to normal experimental procedures for a period of 2 years, demonstrated functional independence of thyroid and adrenal cortical secretions when subjected to stress.