This paper describes the design, synthesis, and characterization of a hydrogen-bonded molecular duplex (3.4). Two oligoamide molecular strands, 3 and 4, with the complementary hydrogen-bonding sequences ADAADA and DADDAD, respectively, were found to form an extremely stable (K-a = (1.3 +/- 0.7) x 10(9) M-1) molecular duplex (3.4) in chloroform. Evidence from 1D and 2D H-1 NMR spectroscopy, isothermal titration calorimetry, and thin-layer chromatography confirmed the formation and the high stability of the duplex. The exceptional stability is explained by positive cooperativity among the numerous hydrogen-bonding and van der Waals interactions and the preorganization of the individual strands by intramolecular hydrogen bonds. This design has opened a new avenue to supramolecular recognition units with programmable specificities and stabilities.