Recently, we have identified specific mutations in transmembrane domain I (TMI) and TMIV of the α1b adrenoceptor that have an effect on its quaternary organization as well as in its binding characteristics. In such studies, performed in transiently transfected HEK293 cells, we also detected that the TMI-TMIV mutations affected receptor localization. The mutant receptor was retained inside the cell rather than delivered to the plasma membrane as the wild type receptor and, therefore, failed to generate any intracellular signal. Mutations deriving to intracellular retention as well as the ability of some chemicals and/or specific ligands to recover cell surface expression have been described for various GPCRs(Ref.1). In order to evaluate the consequences of the ER retention as well as the possibility to regain cell surface delivery and function of the mutant receptor, we used cell lines stably expressing either the wild type or mutant α1b adrenoceptors. In this system we observed: 1-. α1b receptor antagonists are able to rescue the plasma membrane delivery of the mutant receptor. 2-. Prazosin-induced relocation is related to the glycosylation pattern of the mutant receptor 3-. Antagonist-recovered receptor partially recovered the mutant receptor functionality 4-. The differing ligand binding properties between wild type and mutant receptor are due to the mutations per se. and 5-. Native gels show a different quaternary organization of the mutant receptor that shifts to the wild type one when treated with prazosin. These results therefore suggest a link between mutations affecting the molecular organization of some GPCRs and their consequences on receptor localization and function. In addition, we also provide another example of cell surface rescue and function recovery by a specific α1b -adrenoceptor antagonist.