A variety of 18-membered cyclodepsipeptides with alternating repeats of aromatic (phenyl or pyridyl) and Ser units in the ring have been synthesized and studied by X-ray crystallography for self-assembly patterns. Single-crystal structures of the macrocycles showed similar, relatively flat-ring structures. Those molecules containing one or two pyridine units showed self-assembly by stacking one over the other, thus creating tubular structures using aromatic pi-pi interactions between Ph/Pyr or Pyr/Pyr as the main organizing force. The cylindrical stacks are further stabilized by water molecules acting as bridges in intermolecular hydrogen bonding. In both the macrocycle 4b, a hybrid of benzene and pyridine units connected through ester and amide bonds, respectively, and the macrocycle 4d with two pyridine units, the molecules form parallel cylindrical stacks wherein the aromatic rings interdigitate from one column to a neighboring one with a similar to 3.5-Angstrom separation between the planes of the rings. Macrocycle 4a, with two phenyl rings, packs in a herringbone fashion and does not form any tubes. Macrocycle 4a does not exhibit any internal hydrogen bonds. Only 4d forms a tube with an inner space large enough to accommodate a water molecule.