This is an overview of our studies on insulin and insulin-like growth factor-I (IGF-I) interactions with their own and each other's receptors in the lamprey (Lampetra fluviatilis L.), an extant representative of the ancient vertebrate group of Agnathans as compared to mammal (rat). Lamprey insulin receptor shows species specificity, namely, it binds its own insulin with higher affinity than mammalian hormone. Nevertheless, and unlike mammalian insulin receptor, lamprey receptor discriminates relatively poorly between insulin and IGF-I. Autophosphorylation patterns are identical for both receptors. In contrast, IGF-I receptors in lamprey tissues are very similar to mammalian IGF-I receptors confirming known evolutionary conservatism of IGF receptor system. Presumed common evolutionary origin of insulin and IGF-I receptors and poor ability of lamprey insulin receptor to discriminate between two ligands, implies that lamprey insulin receptor is closer to putative ancestral protein that IGF-I receptor. Contrary to the common belief, ambient temperatures for lampreys (4-15 degrees C) put no constraints on either downregulation of receptors or the endocytosis of hormone-receptor complexes.