In a previous article, we demonstrated that the structure-activity relationship model for the mutagenic potency of aromatic amines is different from that for discriminating between mutagens and nonmutagens. In this work, we present further analyses on the molecular determinants of the mutagenicity of aromatic amines. Based on the use of various methodological approaches, our results indicate that mutagenic activity is influenced by different molecular characteristics in different subclasses of aromatic amines. Thus, the general lesson of this article is that 1) in genetic toxicology, it is necessary to separately investigate the structure-activity relationships for discrimination between positive and negative chemicals, and the structure-activity relationships for the potency of the positive chemicals; 2) in structure-activity studies, it is necessary to investigate the degree of homogeneity (congenericity) of apparently similar chemicals in order to assess and describe the various mechanisms of action that may be elicited by the chemicals.