The solubilizing ability of two aromatic hydrotropes, N,N-diethylnicotinamide (DENA) and N,N-dimethylbenzamide (DMBA), was investigated using a set of 13 poorly soluble, structurally diverse drugs. The number of aromatic rings in the solute molecule has a very strong effect on the solubility enhancement produced by either hydrotrope. However, although solubility enhancements in the order of 1000- to 10,000-fold were obtained with each of the hydrotropic agents, important differences were found between the two. DMBA is more hydrophobic and undergoes more extensive self-association than DENA, as determined by vapor osmometry. As a result, DMBA is generally a more powerful solubilizer of hydrophobic drugs. DENA, on the other hand, is more polar and its self-association is essentially limited to dimer formation. However, despite being less hydrophobic, DENA is an extremely powerful solubilizer of paclitaxel, a highly hydrophobic compound. Such a result is attributed to the higher hydrogen bonding ability of DENA over DMBA and the very high hydrogen bonding ability of paclitaxel. These observations in turn illustrate the strong interplay between specific and hydrophobic interactions on the observed solubilization by hydrotropic agents.