Background and objectives: Alpha-2 agonists offer useful effects that make these drugs an interesting alternative for pharmacological premedication.Methods: In a randomized, double-blind study, effects of clonidine (150 [mu]g orally), midazolam (7.5 mg orally) and placebo administered 60-90 min prior to estimated anaesthesia induction time were investigated in 60 healthy ASA I or II patients. All patients received dipotassiumchlorazepate the evening before surgery. At predefined time points, effects of premedication on bispectral index, sedation score and visual analogue scales for anxiety and pain, cognitive function and stress hormones were determined.Results: Administration of low-dose clonidine was associated with slightly lower bispectral index scores than a standard dose of midazolam or placebo. There were no significant differences in sedation score, visual analogue scale for anxiety and pain and cognitive function between treatment regimens. Clonidine, but not midazolam, reduced anaesthetic requirements for induction of anaesthesia and prevented an increase in heart rate as well as an increase in adrenocorticotropic hormone plasma levels during the preoperative period (P <0.05 vs. placebo). Clonidine administration did not delay postoperative recovery.Conclusion: Clonidine augmented haemodynamic stability and partially blunted stress responses as determined by adrenocorticotropic hormone plasma levels. In addition, clonidine did not delay postoperative recovery. Therefore, surrogate parameters indicate that preanaesthetic medication with clonidine may be superior to midazolam in healthy individuals. Further studies have to confirm these results with regard to outcome parameters.