BACKGROUND: There is a significant body of evidence to suggest that hormone levels, receptor density and structural differences between males and females can significantly alter renal hemodynamics. We compared the renal hemodynamic and excretory profile of female and male spiny mice under baseline conditions and in response to a high-NaCl diet. METHODS: Adult male and female spiny mice were fed either a normal or high salt diet for 7 days. Renal excretory profile was obtained from 24 h urine samples, and renal hemodynamic measurements using anaesthetised renal clearance techniques. Kidneys were excised, weighed and frozen for qPCR analysis. RESULTS: Under basal conditions, conscious and anaesthetised renal functions were similar between male and female spiny mice when adjusted for body weights. Male and female spiny mice on the high-NaCl diet had significantly greater GFR than sex matched controls (PDIET <0.001). However the magnitude of the effect of salt was sex dependent (PSEX <0.001; PINT <0.01). Male spiny mice showed a greater increase in GFR (84 higher than normal salt males) compared to females (33 higher than normal salt females), despite similar increases in renal plasma flow. In response to 7 days of high salt diet, female spiny mice showed a greater increase in 24-hour water consumption (45 more) and urinary output (50 more) compared to males (PINT <0.01). These sex differences could not be explained by differences in renal expression of the V2R or AQP3 channel. CONCLUSION: These studies have identified major differences between male and female spiny mice in their renal response to a high-NaCl load suggesting that renal hemodynamics may be differentially regulated for the sexes.