We compared the effects of single doses of etomidate and thiopentone on adrenocortical function in a randomised controlled clinical trial involving 35 critically ill patients who needed a general anaesthetic. Just before induction of anaesthesia, a baseline blood cortisol sample was taken. Twenty-four hours later we performed a short adrenocorticotrophic hormone stimulation test. No patient had a low cortisol level (< 160 nmol.l-1) at any time during the study. Baseline, pre-ACTH and post-ACTH cortisol levels were similar in the two groups. However, significantly more patients in the etomidate group had an ACTH-stimulated cortisol increment < 200 nmol.l-1. The clinical significance of these findings is not clear, but we conclude that single doses of etomidate may interfere with cortisol synthesis for at least 24 h in the critically ill.