The androgen receptor (AR) is required for the development of the male phenotype and traits. Some compounds, including diphenylethers and diphenylamines, inhibit AR activity by binding to a surface cleft named binding function 3 (BF-3). Such inhibitors bind by hydrophobic interactions between the two phenyl groups and the BF-3 site. A similar diphenyl group structure is found in 4,4′ DDT, 4,4′ DDE, 4,4′ DDD, and 2,4′ DDD, which have a diphenylethane or diphenylethylene scaffold. The effect of DDT and related compounds on tritiated dihydrotestosterone (3H-DHT) binding to the AR ligand binding domain (LBD) was measured using a filter binding assay. Results showed that DDT and related compounds inhibited DHT from binding to the AR LBD with IC50 values ranging from 2 to 10 uM, under these conditions. Further analysis showed that DDT and related compounds induce the release of bound DHT from the AR LBD, with IC50 values ranging from 54 to 82 uM. These results suggest that DDT and related compounds may act as endocrine disrupting chemicals and allosterically regulate AR activity by binding to the BF-3 site and blocking binding of the steroid to the ligand binding domain.