Because of the uncertainty in food resources in nature, all animals face the possibility of imposed periods of fasting (i.e., starvation) at some point in their lives. I investigated physiological and biochemical responses to starvation that occur in a species of rattlesnake known to tolerate successfully prolonged periods of starvation in the wild. Sixteen subadult Crotalus atrox were fasted for up to 24 wk under controlled conditions simulating their active season. Snakes exhibited significant reductions in plasma glucose but increased circulating ketone bodies. Fasting snakes lost mass at a linear rate and increased their relative moisture content during the experiment. The bodies of fasting snakes demonstrated an increase in their fatty acid (FA) unsaturation index and were apparently able to "spare" essential FAs effectively from beta -oxidation. Endogenous essential and nonessential amino acids were used indiscriminately to fuel energetic requirements, suggesting that essential amino acids are not preferentially spared during starvation. The (15)N signature of excreted nitrogenous waste increased significantly, presumably as a result of shifting amino acid source pools during starvation. Because our comparative knowledge of starvation physiology contains large taxonomic gaps, particularly with respect to amphibians and reptiles, an understanding of the biological responses exhibited by these animals may offer insight into the evolution of physiological strategies animals employ to cope with the pressures of starvation.