To examine the effect of a decrease in plasma cortisol level on intraocular pressure, 14 subjects with elevated ocular pressure were given oral metyrapone tartrate (an inhibitor of adrenal cortisol biosynthesis) and a placebo in a double-masked, two-period, crossover trial. Ocular pressure and the adrenal response were monitored over a seven-hour period. The decrease in ocular pressure after metyrapone administration was significantly greater than that after placebo. The 14 subjects could be designated as responders or nonresponders by decline of ocular pressure after metyrapone administration compared with response after placebo. The responders could be further differentiated from the nonresponders by a smaller decrease in ocular pressure over time in response to the placebo and by a smaller decrease over time of plasma cortisol level in response to metyrapone. These results provide further evidence that plasma glucocorticoids may play a role in the regulation of ocular pressure.