The small intestine of Burmese pythons, Python molurus bivittatus, undergoes a remarkable size increase shortly after feeding. We studied the dynamics, reversibility and repeatability of organ size changes using noninvasive imaging techniques. We employed light and electron microscopy, flow cytometry and immunohistology to study the cytological mechanisms that drive the size changes of the small intestine. Within 2 days of feeding, the size of the small intestine increased to up to three times the fasting value. The size changes were fully reversible and could be elicited repeatedly by feeding. These enormous size changes were possible because the mucosal epithelium of the small intestine is a transitional epithelium that allows for considerable size changes without cell proliferation. Histological evidence suggested that a fluid pressure-pump system (lymphatic, blood pressure) was the driving force that inflated the intestinal villi. The rates of cell proliferation were not elevated immediately after feeding but peaked 1 week later when small intestine size was already declining. In contrast to the current paradigm, we suggest that the small intestine is not part of the previously proposed 'pay-before-pumping' model. Instead, the size of the python's small intestine may be upregulated without major metabolic investment. It can occur even if the individual is energetically exhausted. An evolutionary perspective of the transitional epithelium mechanism suggests superior functionality compared with the pay-before-pumping model because it allows for long periods of fasting and depletion of energy reserves, while still enabling the snake to digest prey and absorb nutrients.