The alpha adrenoceptors may be subdivided based on their anatomical distribution within the synapse. Presynaptic alpha adrenoceptors are generally of the alpha 2 subtype and modulate neurotransmitter liberation via a negative feedback mechanism. Postsynaptic alpha adrenoceptors are usually of the alpha 1 subtype and mediate the response of the effector organ. Although this anatomical subclassification is generally applicable, many exceptions are now known. A more useful classification of alpha-adrenoceptor subtypes is based on a pharmacological characterization in which selective agonists and antagonists are used. Two major classes of alpha-adrenoceptor agonists are known: the phenethylamines, which are structurally related to norepinephrine, and the imidazolines, which are structurally related to clonidine. A number of important differences between these two classes of agonists have been observed and have led to the conclusion that the phenethylamines and imidazolines interact differently with alpha adrenoceptors. Many developments have recently been made in regard to peripheral alpha adrenoceptors in the cardiovascular system. Postsynaptic alpha adrenoceptors in the vasculature represent a mixed population of alpha 1 and alpha 2 adrenoceptors. Both alpha-adrenoceptor subtypes mediate vasoconstriction, but appear to do so through different mechanisms. alpha 1 adrenoceptors also exist in the heart and mediate a positive inotropic response. Renal alpha 1 and alpha 2 adrenoceptors have been identified and subserve a variety of functions such as regulation of renal blood flow, gluconeogenesis, renin release, and sodium and water reabsorption.