The crystal structure of a tetraurea picket porphyrin-chloride anion complex has previously shown the anion to be situated between two adjacent ureas and hydrogen bonded via four NH protons (J. Am. Chem. Soc. 1998, 120, 11684-11692). The porphyrin receptor also binds a DMSO molecule and utilizes it as a participant in its anion recognition unit, in a manner similar to enzymes that bind water for use as part of their substrate recognition unit. The bound solvent molecule determines the anion-binding affinity, selectivity, and stoichiometry of binding. With a bound DMSO molecule, the tetraurea picket porphyrin is a highly selective receptor for chloride anion and binds all anions with a 1:1 binding stoichiometry. Absent the buried DMSO molecule, the receptor is selective for phosphate anion and binds chloride and phosphate anions with both 1:1 and 1:2 receptor-anion stoichiometries. Additionally, a remarkable reversal in the selectivity of anion complexation between various picket porphyrin receptors is observed, wherein the binding constant ratios change over 3 orders of magnitude as the receptor's number of urea pickets change from four to two. The latter receptor has no urea pickets available to bind to solvent after complexation with an anion. The results demonstrate that anion complexation with hydrogen-bonding receptors in a competitive solvent is enhanced when a ubiquitous solvent molecule is incorporated into the binding motif. In this way, competitive solvent adds to the overall complexation energy and thereby strengthens binding rather than weakens it, as commonly believed. The results are pertinent to drug design, for they suggest that pharmaceuticals need not be completely desolvated to selectively bind to their biological target when water can be included in the binding motif.