Young pre-hypertensive rats of the Milan strain (MHS) have a faster glomerular filtration rate (GFR) and a higher urine flow in vivo than matched normotensive controls (MNS). Kidneys from both MHS and MNS at different ages were perfused in vitro with cell-free artificial medium, in order to further clarify the nature of these differences, in the absence of extrarenal uncontrolled factors. Isolated kidneys from young MHS showed a faster GFR, a larger tubular Na+ reabsorption and urine flow as compared to matched MNS: such differences endured throughout the 2 h of perfusion. These results support an intrinsic kidney abnormality as causing the above described differences between young rats of the two strains. Isolated kidneys from adult MHS showed faster GFR, higher renal perfusion flow and urine flow, yet similar tubular Na+ reabsorption when compared to MNS. Moreover a faster decay in kidney function was observed in the experiments with MHS. The existence of an extrarenal factor(s) correcting the intrinsic MHS kidney abnormality in vivo is suggested, as no differences were reported in kidney function of intact adult animals.