The distribution of ring systems in public mutagenicity databases is analyzed. An automated enumeration of substructures permits determination of the occurrence of different scaffolds in data sets. The counts are used to perform population analysis via proportions and odds ratios of mutagenic compounds. Pairwise calculations of odds ratios between scaffolds allow comparison of ring systems for isostere replacement studies. These findings are presented in tables that readily show which scaffold is likely to occur in mutagenic compounds. Also, rings identified in public domain mutagenicity data sets are compared to rings in drugs data sets; unfortunately, public mutagenicity data sets do not reflect the types of scaffolds in drugs and those typically used in medicinal chemistry. The findings bring into question the utility of predictive models that were derived from public domain data sets. The automated ring identification and statistical approaches used here can be applied to other pharmacological properties to yield information about chemical scaffolds.