Agonist stimulation of G-protein coupled receptors (GPCRs) results in the redistribution of the receptor from the cell surface into intracellular compartments through the process of endocytosis. Monitoring ligand-mediated internalization of GPCRs in living cells has become experimentally accessible by applying fluorescent reagents and fluorescence microscopy. By using cell lines that transiently, stably or endogenously express the human Y receptor (hYR) subtypes hY(1)R, hY(2)R, hY(4)R and hY(5)R and differently fluorescently tagged receptor proteins we were able to unravel further details concerning the internalization behavior of this multi-receptor/multi-ligand system. For the first time we could show that also the hY(2)R is internalized with a rate which is comparable to the hY(1)R and the hY(4)R. In contrast, the hY(5)R was internalized much slower and the rate remained unaffected by co-expression with other hYR subtypes. Furthermore receptor subtype co-expressing cells and selectively binding peptides revealed a receptor subtype selective internalization. By using novel hY(5)/hY(2) receptor chimera the receptor subtype dependent differences in hY receptor internalization could be identified on a molecular level.