We recently reported that tyramine caused concentration-dependent relaxation of rat aorta, which was endothelium independent and was not exerted via α1-adrenoceptors (AR), α2AR, β1AR, β2AR, or receptors for 5-hydroxytryptamine, histamine, and adenosine. The present studies were done on endothelium-denuded strips to determine structure – vasorelaxant activity after blockade of βAR by propranolol plus irreversible blockade of α1AR with benextramine. Vasorelaxation under these conditions was limited to noncatecholamines, and their vasorelaxant potencies were methoxyphenamine > tyramine >p-hydroxyephedrine >L-amphetamine >L-ephedrine > phenylethylamine > synephrine > methoxamine > octopamine. β3AR agonists (BRL 37344 and CGP 12177A) did not produce vasorelaxation, although tyramine could compete for cyanopindolol binding to murine L cells expressing human β2AR or β3AR. There was no significant specific binding of [3H]tyramine to aortic membrane preparations after the inhibition of monamine oxidase. Yohimbine, which has a high affinity forDrosophilatyramine receptors, also caused dose-dependent vasorelaxation like tyramine. It is concluded that tyramine and several other phenylethylamines produce relaxation of rat aorta, which does not involve any of the known adrenoceptors but may be exerted via novel tyramine receptors.Key words: tyramine, phenylethylamines, yohimbine, β3-adrenoceptors, vasorelaxation.