Psammomys obesus lives in an arid environment and feeds on saltbush. When animals are fed a laboratory diet, urine osmolarity drops. To explore the mechanism(s) of water conservation, we measured renal function, kidney solute content, Na-K-ATPase activity, and mRNA in several groups: group I (saltbush diet, 18 g/day, 4.2 g protein); group II (laboratory diet, 10 g/day, 1.8 g protein); and group III, the same as group I, and group IV, the same as group II, both plus a 1-day fast. Urine osmolarity was 2,223 ± 160, 941 ± 144, 1,122 ± 169 and 648 ± 70.9 mosM in groups I, II, III, and IV, respectively. Tissue osmolarities in cortex, outer medulla, and inner medulla, respectively, were 349 ± 14, 644 ± 63, and 1,152 ± 34 µosM/mg tissue in group I; 317 ± 24, 493 ± 17, and 766 ± 60 µosM/mg tissue in group II; 335 ± 6, 582 ± 15, 707 ± 35 µosM/mg tissue in group III; and 314 ± 18, 490 ± 22, and 597 ± 29 µosM/mg tissue in group IV. There were no differences in Na-K-ATPase activity and mRNA in cortex and in medulla between groups I and II, whereas in group III Na-K-ATPase activity and mRNA increased in cortex and outer medulla. These results suggest a key role for urea in corticomedullary osmotic gradient of Psammomys. The absence of differences in Na-K-ATPase activity and mRNA between groups I and II despite differences in tissue sodium concentrations is consistent with Na-K-ATPase-independent Na absorption. Increased Na-K-ATPase activity and mRNA in fasting suggest transition to Na-K-ATPase- dependent Na transport.