Monensin (1) is a representative compound of polyether ionophore antibiotics, which selectively transport Na⁺ ions. In order to obtain potent Na⁺ ionophores, the modification of the carboxyl group of monensin was carried out to yield monensylamino acids (2) and monensylamino acid-1, 29-lactones (3). The Na⁺ permeability of ion through the erythrocyte membrane of 2 and 3 was evaluated by the ²³Na-NMR method. Compound 2 showed less Na⁺ ion transport activity than monensin, probably due to the lower lipophilicity caused by the conformational change of the chain moiety of the molecules. Although 3 showed higher lipophilisity than 1, 3 had no Na⁺ ion permeability, probably due to loss of the carboxyl group. As more lipophilic compounds possessing a carboxyl group was supposed to have more ion transport activity, 7-O-acylmonensins (8) and 7-O-alkylmonensins (11) were synthesized. Among these compounds, the value of Na⁺ ion permeability of 7-O-benzylmonensin (11c) was 1.4 time that of 1. Further investigation was carried out by preparing various 7-O-(substituted benzyl) monensins (13), and 7-O-(p-ethylbenzyl) monensin (13b) exhibited the largest Na⁺ ion permeability, about twice the value of 1. In order to convert monensin (1) to Ca²⁺ ionophore, 7-carboxylmethylmonensin (18) via protected 7-oxomonensin (15), and 25-carboxylmonensin (26) were prepared. In the course of the synthesis, 15 was clarified as a useful intermediate to give 7-amino and 7-alkyl derivatives. Ca²⁺ ion transport activities of 18 and 26 were determined by a CHCl₃ liquid membrane system. 25-carboxylmonensin (26) showed 70% of the activity of Ca²⁺ ionophore, lasalocid A, and compound 26 could be the lead compound for the preparation of a new Ca²⁺ ionophore.