In a prospective controlled trial we studied the effect of a single induction dose of etomidate or thiopentone on the adrenocortical function in 29 patients undergoing elective surgery. During anesthesia and in the recovery period serum cortisol rose significantly in the thiopentone group only. In contrast, after induction with etomidate serum cortisol decreased and remained below the starting values throughout the study period (5 h). The differences between the two groups were significant at 120, 150, 180, 210, and 240 min after induction (p less than 0.05). Moreover, plasma ACTH increased significantly more after etomidate than after thiopentone (p less than 0.02) indicating relative unresponsiveness of the adrenal cortex to stimulation by endogenous ACTH. We conclude that a single i.v. bolus of etomidate (0.26 mg/kg) leads to significant adrenal insufficiency in patients without preexisting endocrine abnormalities.