Phosphatidylcholine vesicles harboring three novel ionophores, based on the condensation of Kemp’s triacid with aromatic diamine spacers, rapidly and selectively extract Pb2+ from 5 ppm aqueous solutions. Encapsulated nitrilotriacetate, a strong water-soluble chelating agent, provides the driving force for divalent metal ion uptake. At acidic to neutral pH, these metal-sorbing vesicles exhibit more than 100-fold greater initial permeability to Pb2+ than to Cd2+. In competitive metal ion uptake studies, Zn2+ and Cu2+ were taken up more readily than Cd2+, although more slowly than Pb2+. The measured initial permeabilities for these systems containing the synthetic carriers were similar to those for vesicles containing the natural ionophore, A23187, yet showed much greater selectivity for Pb2+ over Cd2+. The selectivity of metal-sorbing vesicles is determined by the complex interplay of the metal ion binding and transport characteristics of the ionophore as influenced by the vesicle bilayer microenvironment as well as encapsulated chelator binding.