Endocrine disruptors have recently been shown to promote an epigenetic transgenerational phenotype involving a number of disease states (e.g. male infertility). The anti-androgenic fungicide vinclozolin was found to act transiently at the time of embryonic sex determination to promote in the F1 generation a spermatogenic cell defect and sub-fertility in the male. When the animals were allowed to age up to one year a number of other disease states developed. This phenotype was transferred through the male germ-line to all subsequent generations analyzed (F1-F4). The ability of an environmental factor (i.e. endocrine disruptor) to promote an epigenetic transgenerational phenotype impacts the potential hazards of environmental toxins, mechanisms of disease etiology and evolutionary biology. The biological importance of the epigenetic actions of environmental agents is reviewed in the context of the primordial germ cell and development of epigenetic transgenerational phenotypes.