Virtual high throughput screening (VHTS) was performed to assess possible interactions which might occur between commercially available triphenylphosphonium (TPP) cations and estrogen receptor α (ERα) that could be exploited to design novel ERα modulators. One application of TPP cations is for delivering bioactive molecules to targets in mitochondria as the large membrane potential of mitochondria leads cations to accumulate inside them. The estrogen receptors (ERs) α and β, normally activated by the endogenous hormone 17β-estradiol, are responsible for controlling transcription of nuclear DNA necessary for human development and reproduction. ERs are also associated with the plasma membrane and have been found in the mitochondria of a variety of cell types. Selective estrogen receptor modulators (SERMs) are synthetic compounds which are used to modulate ER activity. Different SERMs display varying combinations of agonistic, antagonistic and neutral effects upon estrogen receptors depending upon the tissue type and cellular location of the receptor. Thus, they are being employed to treat a range of ER-related disorders. A common feature shared by many SERMs is the close arrangement of three aromatic rings similar to TPP cations. Given this structural similarity, the estrogenic activity of triphenyl phosphonium salts was investigated using the automated docking program eHiTS.  Compounds were docked into ten different crystal structures of ERα. Structures were chosen based upon eHiTS ability to accurately identify the majority of estrogenically active compounds given a set of active and decoy molecules. The results of the VHTS suggest hybrids of TPP cations and known SERMs could serve as potent mitochondrial SERMs.