Two derivatives, 3L and 9L, of a ditopic, multiply hydrogen-bonding molecule, known for more than a decade, have been found, in the solid state as well as in solvents of low polarity at room temperature, to exist not as monomers, but to undergo a remarkable self-assembly into a complex supramolecular species. The solid-state molecular structure of 3L, determined by single-crystal X-ray crystallography, revealed that it forms a highly organized hexameric entity 3L6 with a capsular shape, resulting from the interlocking of two sets of three monomolecular components, linked through hydrogen-bonding interactions. The complicated 1H NMR spectra observed in o-dichlorobenzene (o-DCB) for 3L and 9L are consistent with the presence of a hexamer of D3 symmetry in both cases. DOSY measurements confirm the hexameric constitution in solution. In contrast, in a hydrogen-bond-disrupting solvent, such as DMSO, the 1H NMR spectra are very simple and consistent with the presence of isolated monomers only. Extensive temperature-dependent 1H NMR studies in o-DCB showed that the L6 species dissociated progressively into the monomeric unit on increasing th temperature, up to complete dissociation at about 90 °C. The coexistence of the hexamer and the monomer indicated that exchange was slow on the NMR timescale. Remarkably, no species other than hexamer and monomer were detected in the equilibrating mixtures. The relative amounts of each entity showed a reversible sigmoidal variation with temperature, indicating that the assembly proceeded with positive cooperativity. A full thermodynamic analysis has been applied to the data.