This study investigated the effects of increasing plasma concentrations of dexmedetomidine in humans. Ten healthy men underwent intravenous target infusions of dexmedetomidine at concentrations of 0.5, 0.8, 1.2, 2.0, 3.2, 5.0, and 8.0 ng/ml. Hemodynamic, blood gas, and psychometric tests were performed at rest and during the infusions. The results showed that dexmedetomidine decreased catecholamines, increased sedation, and reduced mean arterial pressure. Higher doses led to increased sedation, lower heart rate, and reduced cardiac output. Memory recall and recognition decreased at doses above 0.7 ng/ml. The cold pressor test response was attenuated with increasing doses, and baroreflex heart rate slowing was potentiated. Dexmedetomidine had minimal effects on respiratory variables and acid-base balance. The study concluded that increasing concentrations of dexmedetomidine in humans resulted in progressive increases in sedation and analgesia, decreases in heart rate, cardiac output, and memory. A biphasic dose-response relation was observed for mean arterial pressure, pulmonary arterial pressure, and vascular resistance. Dexmedetomidine is a full agonist of the α₂ receptor, which may allow its use in high doses for sedation and analgesia without unwanted vascular effects from α₁ receptor activation. The study also found that higher concentrations of dexmedetomidine caused systemic and pulmonary hypertension, but with minimal respiratory changes. The cardiovascular effects might limit the usefulness of high concentrations in less healthy patients. The study highlights the dose-dependent effects of dexmedetomidine on sedation, analgesia, and cardiovascular function.This study investigated the effects of increasing plasma concentrations of dexmedetomidine in humans. Ten healthy men underwent intravenous target infusions of dexmedetomidine at concentrations of 0.5, 0.8, 1.2, 2.0, 3.2, 5.0, and 8.0 ng/ml. Hemodynamic, blood gas, and psychometric tests were performed at rest and during the infusions. The results showed that dexmedetomidine decreased catecholamines, increased sedation, and reduced mean arterial pressure. Higher doses led to increased sedation, lower heart rate, and reduced cardiac output. Memory recall and recognition decreased at doses above 0.7 ng/ml. The cold pressor test response was attenuated with increasing doses, and baroreflex heart rate slowing was potentiated. Dexmedetomidine had minimal effects on respiratory variables and acid-base balance. The study concluded that increasing concentrations of dexmedetomidine in humans resulted in progressive increases in sedation and analgesia, decreases in heart rate, cardiac output, and memory. A biphasic dose-response relation was observed for mean arterial pressure, pulmonary arterial pressure, and vascular resistance. Dexmedetomidine is a full agonist of the α₂ receptor, which may allow its use in high doses for sedation and analgesia without unwanted vascular effects from α₁ receptor activation. The study also found that higher concentrations of dexmedetomidine caused systemic and pulmonary hypertension, but with minimal respiratory changes. The cardiovascular effects might limit the usefulness of high concentrations in less healthy patients. The study highlights the dose-dependent effects of dexmedetomidine on sedation, analgesia, and cardiovascular function.