Besides the important role of the Major Histocompatibility Complex (MHC) class I molecules n physiologically restricting immune responses, they seem to play a non-immunological function by the molecular association with several hormone receptors (R). Among the hormone R and class I antigen (Ag) interactions, insulin R, epidermal growth factor (EGF) R, interleukin-2 (IL-2) R, luteinizing (LH) hormone R, beta adrenergic R and muscarinic cholinergic R were described in several human and animal models. Evidences from immunoprecipitation assays, binding assays and immunofluorescence techniques pointed to the molecular association of all of these R with class I molecules on cellular surfaces. Only for beta adrenergic R, muscarinic cholinergic R and LH-R, antibodies directed against class I products were described to exert the activation of these R leading to the production of intracellular second messengers and consequently modifying the physiology of the corresponding cell. This was also obtained on insulin R with peptides derived from class I molecules. The selectivity or R involved in all studied cellular types, should find its explanation in the physiological importance of the considered R for the indicated cell. The participation of cytoskeletal proteins on these interactions and the proximity on cell surfaces between both molecules, probably managed by ligand-mediated microaggregation, are also facts to be taken into account to better understand the biological consequences of these interactions.