Conformational analyses of large molecules as fatty acids and triglycerides are usually amenable by molecular mechanics. A correct evaluation of the electrostatic energy term is thus crucial in determining reliable results. In this contribution, we have considered the most abundant fatty acids in biomembranes, i.e., lauric, stearic, oleic, and elaidic acid, and the corresponding triglycerides, i.e., trilaurin, tristearin, triolein, and trielaidin, and estimated the Mulliken and potential‐derived charges both at the semiempirical AM1 and ab initio HF MO STO‐3G level. Atomic charges obtained by the Mulliken population analysis do not take into account the full geometry of the molecule. On the contrary, the change of conformation, due to different chains length or the presence of a trans or cis double bond, greatly influences the repartition of the potential‐derived charges. A systematic comparative analysis shows that charges calculated by AM 1 are not suitable because as they do not reproduce potential‐derived charges obtained by ab initio. © 1993 John Wiley & Sons, Inc. Copyright © 1993 John Wiley & Sons, Inc.