1. The pharmacodynamic effects of medetomidine, a novel alpha 2-adrenoceptor agonist, are reviewed. 2. In receptor binding experiments, and in isolated organ preparations medetomidine shows high specificity and selectivity to alpha 2-adrenoceptors. Its alpha 2/alpha 1 selectivity ratio is 1620 compared to 220 of clonidine. It is a highly potent full agonist at alpha 2-adrenoceptors, a fact that also distinguishes it from clonidine. 3. Medetomidine induces a dose-dependent decrease in the central release and turnover of norepinephrine (NE) measured as changes in metabolite concentrations or using pharmacological intervention techniques. 4. The selectivity, specificity and potency of medetomidine is further supported by various in vivo experiments showing dose-dependent hypotensive, bradycardic, sedative, anxiolytic mydriatic, hypothermic and analgesic effects. 5. The pharmacological, neurochemical and behavioral effects of medetomidine can be inhibited by prior, simultaneous or subsequent administration of selective and specific alpha 2-antagonists. 6. In humans medetomidine is well-tolerated and pharmacodynamic effects including e.g. dose-dependent decrease of vigilance, blood pressure, heart rate, salivary secretion and plasma NE are compatible with an agonistic action at alpha 2-adrenoceptors.