The spontaneously hypertensive rat has an exaggerated preference for salt solutions, which has led to the suggestion that this model seeks out solutions that provide a volume stimulus to the circulation, contributing to the development of hypertension (1). Rats exposed to protein restriction in utero develop hypertension and renal dysfunction (2), but it is not known whether sodium homeostasis is perturbed in this model. Accordingly, the aim of this study was to assess salt appetite, sodium homeostasis and expression of key renal sodium transporters in male rats exposed to protein restriction in utero. Female Wistar rats were given a diet containing 18% (control, C) or 9% casein (low protein, LP) from day one of conception until birth. Mothers were then switched to a standard rat chow containing 18% protein; pups were weaned onto this diet. At 4 weeks of age, rats were housed individually and offered a two-bottle choice of either tap water or 0.9% saline for 6 days. Extracellular fluid (ECF) volume was determined in another group of rats. Under Inactin anaesthesia (thiobutabarbital sodium, 100 mg/kg, i.p.) the renal vessels were occluded and ³H inulin was injected (i.v.); serial blood samples were collected to determine the dilution of ³H inulin. A third group of Inactin anaesthetised (100 mg/kg, i.p.) rats were also prepared for a standard clearance study using a servo-controlled fluid replacement system. Saline (0.9%) was infused (i.v.) at a rate matching spontaneous urine output. Kidneys were harvested, post mortem, from a further group of rats for Western blotting and measurement of Na⁺-K⁺,ATPase activity to estimate key Na⁺ transporter expression and function. Data are presented as mean ± SEM; statistical analysis was by t test. LP rats drank significantly more saline than controls (C 4.8±1.8 vs LP 9.4±1.1 ml (100g bwt)^-1 24h^-1, P<0.05, n=22-24 per group). ECF volume was significantly larger in LP compared with controls (C 23.5±1.2 vs LP 28.3±1.2 ml (100g bwt)^-1, n=9-13 per group). Blood pressure, urine flow rate (UV), Na⁺ excretion rate (U_NaV) and fractional excretion of Na⁺ (FE_Na) were higher in LP rats, but GFR did not differ (Table 1). Sodium-hydrogen exchanger (NHE3) expression was not altered; however, the sodium-potassium-chloride cotransporter (NKCC2) was upregulated by 135% in the LP group. Na⁺-K⁺,ATPase activity was significantly reduced in LP rats compared with controls (C 23.4±1.7 vs LP 17.7±1.2 nM PO₄ (g protein)^-1 h^-1, P<0.05 , n=10-17 per group). These findings show that sodium homeostasis is disturbed in rats exposed to protein restriction in utero. Renal sodium retention does not appear to be the underlying cause of the expanded ECF volume in LP rats. Rather, an increased salt appetite may contribute to the elevation in blood pressure.