Background: Clomiphene Citrate is composed of two structural isomers: cis- or Zuclomiphene citrate (Zu) and trans- or Enclomiphene citrate (En). Clomiphene, as well as isolate isomers, has recently been shown to have effects on Ebola virus infections. It has been shown that the enclomiphene molecule is an estrogen antagonist and that zuclomiphene is inactive. We demonstrate here that the two isomers have different fates once ingested and the tissues that absorb each are distinct from each other to lead to different biologic effects. Methods and findings: We studied these molecules by employing 14C-labelled versions of each in C-57 black mice. Mice were given the same oral dose, but sacrificed at different time periods. Each isomer could be followed separately. Enclomiphene was rapidly lost such that the majority was found in low amounts after 24 h. Zuclomiphene was distributed to more organs and remained associated with discrete tissues for longer periods of time. Remarkable exceptions were the pigmented organs of the eye, which retained both compounds. Notable was the specific absorption in individual tissues and the lack of clearance in certain cases. The ratio of zuclomiphene to enclomiphene (Zu/En) demonstrated the promiscuous nature of the zuclomiphene and the specific absorption. The tissue/plasma ratios demonstrated those tissues that were accrued or failed to clear compounds. Important differences were found in the lack of clearance of isomers in the eye, gall blabber/bile, brain, lung, fat, adrenals, kidneys and reproductive tissues. Conclusion: The adverse effects of Clomiphene citrate in the eye and male reproductive organs may be rationalized by lack of clearance of higher levels of zuclomiphene as well as effects of Ebola virus infection. An additional element of this study was to determine levels that would not be expected to represent a significant radiation exposure risk to human male volunteers in future ADME studies.