There is growing evidence which suggests that the ovarian hormone relaxin (RLX) contributes to the changes in renal function associated with pregnancy. Studies in male rats have shown that RLX induces an increase in renal blood flow and glomerular filtration rate (1) as well as a diuresis and natriuresis following long- (7 days) but not short-term (2h) administration (2). The aim of this study was to determine whether RLX has similar effects in female rats and to localise expression of the RLX receptor LGR7 in the kidney. Under isoflurane anaesthesia (4% in O₂, 2 l/min), female Sprague Dawley rats were implanted with an osmotic minipump containing human recombinant RLX (0.4 µg/h or 4 µg/h) or vehicle (20 mM sodium acetate). Seven days later, standard renal clearance measurements were made under Inactin anaesthesia (100 mg/kg thiobutabarbital sodium, i.p.). A servo-controlled fluid replacement system was used to maintain a euvolaemic body fluid status. RLX (4 µg h^-1 100g bwt^-1) or vehicle was administered acutely to a second group of anaesthetised rats for a period of 2h under similar euvolaemic conditions. Kidneys were harvested post mortem from separate groups of female rats previously exposed to RLX at 0.4 µg/h or 4 µg/h for 7 days and pregnant female rats (Day 11, corresponding to maximal plasma [RLX]) for Western blotting and immunohistochemistry for the LGR7 receptor. Administration of RLX at 0.4 µg/h for 7 days induced a significant reduction in osmolar excretion and urinary sodium and chloride excretion and clearance rates. Plasma sodium (vehicle 126.5 ± 0.3 vs RLX 105.1 ± 0.8 mmol/l) and chloride (vehicle 112.8 ± 4.5 vs RLX 104.4 ± 2.7 mmol/l) concentrations and plasma osmolality (vehicle 292.6 ± 2.1 vs RLX 236.9 ± 6.1 mosmol/kg) were also reduced. RLX at 4 µg/h for 7 days or acutely for 2 h had no effect on these variables. Statistical significance was assumed at the 5% level. Western blotting revealed LGR7 expression in both the cortex and medulla of control, RLX-treated and pregnant female rat kidneys. LGR7 expression was increased in the kidneys of pregnant rats (control 103±16 vs 217±15 arbitrary units, n = 5, P<0.01) and rats treated with RLX at 0.4 µg/h (178±42, n = 5, P<0.05) but not 4 µg/h. Immunolocalisation showed that LGR7 was present on the proximal tubule and inner medullary collecting duct, in addition to blood vessels. These data show that RLX evokes dose-related changes in renal function in the female rat which, at the lower dose employed, resemble those seen in pregnancy. The lack of effect at the higher dose is consistent with the known desensitisation of RLX receptors following prolonged administration or exposure to high doses (3). Up-regulation of LGR7 expression in kidneys from pregnant rats lends further support to the suggestion that RLX contributes to the changes in renal function seen in pregnancy.