Mammalian guts exhibit numerous adaptive responses to feeding. However, response magnitudes are often inconveniently modest for experimental analysis, because mammals feed often and their intestines are rarely empty. We anticipated larger responses in sit-and-wait foraging snakes, because they consume huge meals at long intervals. Hence, we studied metabolic rates, brush-border nutrient transport, and intestinal morphometrics in the rattlesnake, Crotalus cerastes, as a function of time since feeding. O2 consumption by the whole snake, a reflection of the cost of digestion and of rebuilding the starved gut, peaked after 2 days at eight times fasting values. Activities of brush-border glucose, leucine, and proline transporters peaked after 1-3 days at 5-22 times fasting values. Ratios of amino acid to glucose uptake rates peaked at 104, reflecting snakes' extreme adaptation to carnivory (a high-protein low-carbohydrate diet). Intestinal mass increased more than twofold within 1 day, primarily because of mucosal growth. After defecation, the intestine atrophied, brush-border transporters were downregulated, and O2 consumption returned to basal. These rapid and large responses reduce costs of gut maintenance during long bouts of quiescence between meals. Hence sit-and-wait foraging snakes may furnish advantageous model species for studying gut regulation and adaptation.