Three different QSAR methods, Comparative Molecular Field Analysis (CoMFA), classical QSAR (utilizing the CODESSA program), and Hologram QSAR (HQSAR), are compared in terms of their potential for screening large data sets of chemicals as endocrine disrupting compounds (EDCs). While CoMFA and CODESSA (Comprehensive Descriptors for Structural and Statistical Analysis) have been commercially available for some time, HQSAR is a novel QSAR technique. HQSAR attempts to correlate molecular structure with biological activity for a series of compounds using molecular holograms constructed from counts of sub-structural molecular fragments. In addition to using r2 and q2 (cross-validated r2) in assessing the statistical quality of QSAR models, another statistical parameter was defined to be the ratio of the standard error to the activity range. The statistical quality of the QSAR models constructed using CoMFA and HQSAR techniques were comparable and were generally better than those produced with CODESSA. It is notable that only 2D-connectivity, bond and elemental atom-type information were considered in building HQSAR models. Since HQSAR requires no conformational analysis or structural alignment, it is straightforward to use and lends itself readily to the rapid screening of large numbers of compounds. Among the QSAR methods considered, HQSAR appears to offer many attractive features, such as speed, reproducibility and ease of use, which portend its utility for prioritizing large numbers of potential EDCs for subsequent toxicological testing and risk assessment.