STUDY OBJECTIVE: To study the effect of intravenous (IV) sedation on blood pressure (BP), heart rate (HR), and respiratory rates (RR) to determine if IV sedatives differ with respect to their effect on BP, HR, and RR. DESIGN: Prospective, randomized, single-blinded, placebo-controlled study. SETTING: Monitored patient care room at a clinical research center. SUBJECTS: 60 healthy ASA physical status 1 volunteers. INTERVENTIONS: Subjects were randomized to receive, in increasing doses, one of three IV sedatives: propofol, midazolam, or dexmedetomidine; or saline control. MEASUREMENTS: Blood pressure (systolic, diastolic), HR, and RR were recorded. MAIN RESULTS: A significant dose-dependent BP reduction occurred with dexmedetomidine and, to a lesser degree, with propofol; and there was good agreement of predicted versus measured drug concentrations for all sedatives. Blood pressure and HR of participants who received midazolam did not change. CONCLUSIONS: When administered in sedative doses, dexmedetomidine and, to a lesser extent, midazolam, reduces BP in a dose-dependent fashion. Dexmedetomidine also reduces HR. Midazolam does not affect BP or HR.