A quantitative comparative analysis of molecular electrostatic potential (MEP) distributions generated from different wave functions was carried out. Wave functions were computed by using MNDO, AMl, STO‐3G, 3‐21G, 4‐31G, 6‐31G, 4‐31G*, 6‐31G*, and 6‐31G** methods. Ten different compounds, which include usual atoms and groups of biomolecules, such as hydroxyl, carbonyl, amine, amide, imine, double and triple bonds, and heteroaromatic rings, were studied. For each compound, MEP values in the points of a common 3‐D grid were computed; thereafter, the similarity between each pair of MEP distributions generated by different methods was assessed. Similarities were measured using the Spearman rank correlation coefficient. A similarity matrix was obtained for each compound. Similarity matrices were averaged and a hierarchical cluster analysis was carried out to classify the different quantum chemical methods. In the compounds studied, the main conclusion is the negligible difference between the pattern of MEP distributions generated from all split valence basis sets (with and without polarization functions). © 1993 John Wiley & Sons, Inc. Copyright © 1993 John Wiley & Sons, Inc.