A novel use of NMR chemical shift of the SO(2)NH(2) protons (in dioxane as solvent) as a molecular descriptor is described for modeling the inhibition constant for benzene sulfonamides against the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The methodology is extended to model diuretic activity and lipophilicity of benzene sulfonamide derivatives. The regression analysis of the data has shown that the NMR chemical shift is incapable of modeling lipophilicity. However, it is quite useful for modeling the diuretic activity of these derivatives. The results are compared with those obtained using distance-based topological indices: Wiener (W)-, Szeged (Sz)-, and PI (Padmakar-Ivan) indices.