BACKGROUND: At 27 days of gestation in the ovine fetus (term = 145 to 150 days), the only kidney is the mesonephros, and allantoic fluid represents fetal urine. The hypothesis tested in this study was that functional glucocorticoid receptors (GRs) are present in this early mesonephric kidney. METHODS: Pregnant ewes, between 26 and 30 days, were infused with saline, dexamethasone (0.48 mg/hour), cortisol (5 mg/hour), or aldosterone (10 microg/hour) for 48 hours and were then killed for collection of fetuses and fetal fluids. GR mRNA was measured by real-time polymerase chain reaction in whole fetuses, and the location of gene expression was determined by hybridization histochemistry. RESULTS: Significant changes in allantoic fluid composition were produced by the exposure of the fetus to maternally infused synthetic (dexamethasone) and natural (cortisol) glucocorticoids, over a period of two days, compared with fetuses of ewes infused with vehicle (isotonic saline; N = 8) or aldosterone (N = 8). Volume of fluid was unchanged by any treatment, but both dexamethasone (N = 10) and cortisol (N = 8) caused significant (P < 0.05) decreases in sodium and chloride concentrations and increases in concentrations of potassium, urea, glucose, and fructose. GR mRNA was detected in equivalent concentrations in the whole fetuses of saline, dexamethasone, and cortisol treatments. The GR mRNA levels were significantly decreased in the aldosterone group. By hybridization histochemistry, GR mRNA was detected in most of the tubular cells of the mesonephros. CONCLUSION: These results suggest that functional GRs are present in the early ovine mesonephros.