OBJECTIVE Tubulo-glomerular feedback (TGF) is a key mechanism for controlling glomerular filtration. Nephrectomy for kidney donation provides a good opportunity for studying TGF status before and after a defined loss of renal function. METHODS A total of 22 kidney donors were studied before and one year after nephrectomy. Effective renal plasma flow and glomerular filtration rate were measured by means of para-amino-hippurate and inulin plasma clearances before and after intravenous acetazolamide. RESULTS TGF activation was not dependent on sex, age or familiality for hypertension either before or after nephrectomy, however, it increased the filtration fraction before, but not after nephrectomy. Nephrectomy did not affect TGF response, but elicited a correlation between TGF response and renal plasma flow, not present in the intact state. Donors with a more activated TGF before nephrectomy had a lower filtration fraction that increased after nephrectomy, while subjects with a less activated TGF before nephrectomy had a higher basal filtration fraction that showed a blunted increase after nephrectomy. CONCLUSIONS TGF is a stable mechanism quantitatively unaltered by nephrectomy, age, sex, menopausal status or family history of hypertension. However, its degree of activation before nephrectomy determines different responses to the loss of a kidney.