Pythons are renowned for the profound phenotypical flexibility of their visceral organs in response to ingestion of large meals following prolonged fasting. Traditionally, the phenotypic changes are studied by determining organ mass of snakes killed at different times during digestion. Here we evaluate the use of magnetic resonance imaging (MRI) for in vivo measurements of the visceral organs in fasting and digesting snakes. Twelve snakes were MRI scanned immediately before the organs were removed and weighed to provide direct comparison of the two methods. Both methods provided similar estimates for the mass of liver, gallbladder, and pancreas, whereas MRI overestimated the size of the heart and small intestine, probably because blood and digesta contributed to the volume determined by MRI. The correlations were used to derive wet organ mass from MRI-based volumes to evaluate the mass development through repeated MRI scans of five digesting snakes. MRI was performed at fasting and 24, 48, 72, 132, and 500 h after eating a meal corresponding to 25% of body mass. This observation period revealed a reversible volume upregulation of the visceral organs, supporting the view that successive MRI facilitates in vivo investigations of structural changes accompanied by digestion.