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The desert-adapted spiny mouse has a significantly lower glomerular number, increased glomerular size, and a more densely packed renal papillae compared with the similar-sized laboratory-adapted C57BL/6 mouse. In the present study we examined the functional consequences of these structural differences in young adult male spiny and C57BL/6 mice and detailed the impact of 1 wk of a high-salt (10% wt/wt NaCl) diet. Basal food and water intake, urine and feces production, and urinary electrolyte concentrations were not different between species, although urinary urea concentrations were higher in spiny mice (P < 0.05). On normal salt, MAP of the anesthetized spiny mouse was similar to 18 mmHg lower, effective renal plasma flow ( ERPF) was 40% lower (P < 0.001), and glomerular filtration rate (GFR) tended to be lower than in the C57BL/6 mouse. On the high-salt diet, both species had similar 24-h NaCl excretions; but C57BL/6 mice required a significantly increased amount of water ( lower urine NaCl concentration) than the spiny mice. Filtration fraction was greater in both species on the high-salt diet. Spiny mice had greater GFR and ERPF after the high-salt diet, whereas the C57BL/6 mouse showed little change in GFR. The ability of the spiny mouse to tolerate a significantly higher plasma osmolality after salt, measured by a decreased drinking response, and the ability to increase ERPF at a lower MAP are features that allow this species to conserve water more efficiently than can be done in the C57BL/6 mouse. These features are important, particularly since the desert mouse has a smaller kidney, with fewer nephrons.