In mammals, the sorting of newly synthesized lysosomal enzymes is accomplished by two mannose 6-phosphate receptors (MPR) designated MPR46 and MPR300. MPR300 has an additional function in clearing the nonglycosylated insulin-like growth factor II (IGFII). The distinct expression pattern of the two MPR has been ascribed to the control of MPR300 expression by IGFII. In lower vertebrates, such as chickens or frogs, only MPR300 homologues have been described. These MPR300 homologues do not bind IGFII. In the present study, we examined whether lower vertebrates such as chickens also express two types of MPR and, if so, whether the expression pattern is distinct or similar. We were able to clone chicken cDNA fragments homologous to mammalian MPR46 and MPR300 and to show the synthesis of respective MPR polypeptides, thus establishing the existence of two types of MPR also in a nonmammalian species. Further, we analyzed the expression of the two MPR in chicken by Northern blotting and in situ hybridization. High levels of MPR46 and MPR300 RNA were detectable in epithelia, ganglia, and uropoietic system of chicken embryos. In a number of embryonic and adult tissues, varying ratios of MPR46 and MPR300 RNA were observed. The expression pattern for both MPR46 and MPR300 was distinct, although less pronounced than in mice. We conclude that functional differences unrelated to the additional function of the mammalian MPR300 as a receptor clearing IGFII are responsible for the distinct expression of the two MPR in nonmammalian, and probably also in mammalian, species.