This article examines the medical literature of the sixteenth and early seventeenth centuries concerning the sexual transmutation of females into males. One explanation for the phenomenon, the so-called one-sex model attributed to Aristotle, does not figure prominently in the writings of the early physicians after 1575. That such a transformation was even possible was entirely discounted by 1600. By implication, those studies of Renaissance culture and thereafter, particularly pertaining to the presumed anxiety associated with cross-dressing, are now due for reexamination to the extent that sex change case studies were employed as the basis of that anxiety concerning sexual plasticity and uncertainty.