BACKGROUND Propofol is often used for sedation in the intensive care unit. The aim of this study was to compare the efficacy and endocrine response of propofol vs. the new alpha2-agonist dexmedetomidine for sedation in surgical intensive care patients who need postoperative short-term ventilation. METHODS Our work is a randomized clinical study conducted on sixty adult patients who required postoperative short term ventilation and sedation. The patients were allocated randomly, to receive IV infusion of either dexmedetomidine 0.2-0.5 microg/kg/h or propofol 0.5-1 mg/kg/h. Hemodynamic parameters, Ramsay sedation score, extubation time and serum cortisol and interleukin-6 (IL-6) levels were measured. RESULTS Ramsay sedation score was 4.1+/-1 and 4+/-0.9 for propofol and dexmedetomidine, respectively, (p=0.59.) Total fentanyl dose in the propofol group was 75+/-15 microg compared to 15+/-10.5 microg in the dexmedetomidine group, (p=0.0045). Patients who received dexmedetomidine infusion had significantly lower heart rates compared to patients who received propofol infusion, (p=0.041). Pre-infusion serum concentrations of IL-6 were comparable in both groups, while the 24 h post-infusion levels were insignificantly decreased in both groups compared to pre-infusion level, (p=0.36). There were no intergroup differences in serum cortisol concentrations (p=0.231). CONCLUSIONS Dexmedetomidine and propofol are safe sedative drugs for postoperative mechanichally ventilated patients. Patients were easily aroused to co-operate without showing signs of irritations with less fentanyl analgesia in the dexmedetomidine group. Dexmedetomidine and propofol do not inhibit adrenal function, but they may influence the inflammatory response.