Various types of glaucomatous and normal subjects were tested for the adequacy of the stress response of their hypothalamic-pituitary-adrenal axis to pyrogen and vasopressin. With pyrogen, a significant response of elevation of plasma cortisol levels was positively correlated with ocular pressure and changes of the optic disc. Those subjects with increased ocular pressure and optic disc cupping and pallor had greater rises of plasma cortisol levels. With vasopressin, a decreased response of plasma cortisol levels was negatively correlated with the degree of elevated ocular pressure. Those subjects with increased ocular pressure and lower tonographic outflow facilities had smaller rises of plasma cortisol levels. Both tests indicated a disturbance of the hypothalamic-pituitary-adrenal axis in subjects with glaucoma.