The effects were studied of two i.v. anaesthetics (Althesin and ketamine) on resting and activated adrenocortical function in the rat. Small doses of Althesin and ketamine comparable to those required to produce induction of anaesthesia in man evoked adrenocortical stimulation, but the stressing effects of ketamine were more prolonged. During deep anaesthesia with either anaesthetic there was an inhibition of pituitary adrenal activation induced by handling and surgery. However, during recovery, ketamine was associated with intense and prolonged adrenocortical stimulation. The stress of laparotomy in control rats and in rats pretreated with the anaesthetics caused a depletion of noradrenaline in the hypothalamus; this suggests that both anaesthetics inhibit adrenocortical activation by mechanisms different from adrenergic inhibition.