The reproductive and adaptative behavior of wild rodents is synchronized primarily by the photoperiod. The viscacha, a South American rodent of nocturnal habits and seasonal reproduction is photoperiod-dependent and its reproductive behavior is regulated by the retinohypothalamic-pituitary pineal axis. Adult males exhibit an annual reproductive cycle with periods of maximum gonadal activity (summer-early autumn) and gonadal regression (winter). The corpus and the cauda, the most sensitive segments of the epididymis to changes induced by the photoperiod, were analyzed using electron microscopy and enzymatic biochemistry. During gonadal regression, principal and clear cells showed signs of involution with respect to the activity period. These were characterized by more irregular nuclei, smaller cytoplasms, large vacuoles, altered mitochondria, and glycogen deposits. All cellular populations of the epididymal epithelium in regression presented abundant lysosome-like dense bodies during the active period. In addition, we measured the activity of four acid glycosidases in the cauda epididymis along the reproductive cycle. N-acetyl-beta-D-glucosaminidase (NAG), an enzyme that degrades endocytosed substances from the epididymal lumen, increased significantly during gonadal regression relative to the active period. These results demonstrate that the viscacha epididymis exhibits significant ultrastructural and biochemical changes during the reproductive cycle. We demonstrate that during regression, melatonin secretion in viscacha increases. This study shows that the epididymal epithelium is reduced. Thus, we postulate that the changes observed in the epididymis are modulated by pineal melatonin. Despite these changes, the epididymis might maintain a microenvironment suitable for the survival of stored spermatozoa.