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To test the hypothesis that desert ungulates adjust their physiology in response to long-term food and water restriction, we established three groups of sand gazelles (Gazella subgutturosa): one that was provided food and water (n = 6; CTRL) ad lib. for 4 mo, one that received ad lib. food and water for the same period but was deprived of food and water for the last 4.5 d (n = 6; EXPT1), and one that was exposed to 4 mo of progressive food and water restriction, an experimental regime designed to mimic conditions in a natural desert setting (n = 6; EXPT2). At the end of the 4-mo experiment, we measured standard fasting metabolic rate (SFMR) and total evaporative water loss (TEWL) of all sand gazelles and determined lean dry mass of organs of gazelles in CTRL and EXPT2. Gazelles in CTRL had a mean SFMR of 2,524 +/- 194 kJ d(-1), whereas gazelles in EXPT1 and EXPT2 had SFMRs of and 2,101 +/- 232 kJ d(-1), respectively, values that differed significantly when we controlled for differences in body mass. Gazelles had TEWLs of 151.1 +/- 18.2, 138.5 +/- 17.53, and 98.4 +/- 27.2 g H2O d(-1) in CTRL, EXPT1, and EXPT2, respectively. For the latter group, mass-independent TEWL was 27.1% of the value for CTRL. We found that normally hydrated sand gazelles had a low mass-adjusted TEWL compared with other arid-zone ungulates: 13.6 g H2O g(-0.898) d(-1), only 17.1% of allometric predictions, the lowest ever measured in an arid-zone ungulate. After 4 mo of progressive food and water restriction, dry lean mass of liver, heart, and muscle of gazelles in EXPT2 was significantly less than that of these same organs in CTRL, even when we controlled for body mass decrease. Decreases in the dry lean mass of liver explained 70.4% of the variance of SFMR in food- and water-restricted gazelles. As oxygen demands decreased because of reduced organ sizes, gazelles lost less evaporative water, probably because of a decreased respiratory water loss.