AbstractQSAR models for inhibition of monoamine oxidase (MAO) by aryloxyacetohydrazide derivatives were developed for a series of MO parameters computed with the AM1 Hamiltonian. These models were compared to those based on the recently developed electrotopological state index for. skeletal atoms. The structure interpretation is the same for both types of models: the NH group adjacent to the carbonyl group together with the carbon atom, gamma to the NH group, in the hydrocarbon substituent, account for more than 90% of the computed activity. However, the model based on E‐state indexes (r2= 0.9012) is significantly superior to the one based on MO parameters (r2= 0.7985); the standard deviation for the MO based model (s = 0.27) is 50% larger than that from the E‐state based model (r = 0.19). Several points of comparison between the models are presented. This study supports the idea that the electrotopological state is a useful representation of molecular structure informat