• Values of plasma free cortisol (not bound to plasma proteins), total plasma cortisol, and percent free cortisol were determined in normal, ocular hypertensive, and open angle glaucomatous subjects. Median total plasma, plasma free, and percent free cortisol levels were higher in ocular hypertensive and glaucomatous individuals. The most significant differences occurred with percent free cortisol values between normal and glaucomatous subjects. There was a significant positive correlation between percent free cortisol and total cortisol levels in normal subjects only. For subjects with glaucoma and hypertension, the percent free cortisol values were independent of the total cortisol values. Multilinear regression analysis also indicated that besides diagnosis and level of total plasma cortisol, male sex, blood sampling late in the day, and increased diastolic blood pressure were the only variables significantly related to increased values of plasma free cortisol and percent free cortisol. Ocular medication for glaucoma and use of betablockers were not found to be significant independent variables in the regression models for either plasma free cortisol or percent free cortisol. These observations further suggest that a disorder of the pituitary adrenal axis and/or a binding of plasma cortisol is associated with ocular hypertension and open angle glaucoma.