A linear quantitative structure-activity relationship has been developed for a series of para-substituted aromatic sulfonamides by using topological index methodologies. The compounds were studied for their carbonic anhydrase II (CAII) inhibitory activity. A large series of topological indices were calculated and the stepwise regression method was used to derive the most significant model. Very good results were obtained using multi-parametric regressions and showed that the information approach used in the present work is quite useful for modeling carbonic anhydrase inhibition.