AbstractCentral hypotensive activity of α‐adrenoceptor agonists generally parallels bradycardic potency. This has led to the conclusion that bradycardia, like the induction of hypotension, is also initiated within the central nervous system by stimulation of α2‐adrenoceptors. However, bradycardia has still been found for a very hydrophilic α‐adrenoceptor agonist not showing central hypotensive activity following systemic application. In view of this inconsistency quantitative comparisons were made between central hypotensive activity and overall bradycardic potency in anaesthetized normotensive rats after intravenous administration within a series of phenyliminoimidazolidines. The log dose‐bradycardic response curves of the more lipophilic derivatives were monophasic, whereas those of the hydrophilic compounds were characterized by a bisigmoidal shape. As a result of the dual nature of this effect, the potency of the drugs to decrease heart rate was quantified at 10%, pC10(HR), as well as at 20%, pC20(HR), effect level. Linear regression analysis showed a highly significant correlation between pC20(HR) and hypotensive activity. Lipophilicity, log P′, had to be added to verify this relationship for pC10(HR). For the latter variable, however, a linear relationship was derived with the potency of the compounds to inhibit cardiac frequency via stimulation of presynaptic α2‐adrenoceptors in the heart itself. These results strongly suggest that overall bradycardia of α‐adrenoceptor agonists may consist of a peripheral and a central component. Both mechanisms are governed by the stimulation of α2‐adrenoceptors. The peripheral mechanism (presynaptic cardiac α2‐adrenoceptors) is triggered by hydrophilic as well as lipophilic compounds following systemic application. The induction of central bradycardia (central α2‐adrenoceptors) and hypotension is but limited t