Mechanoreceptors and chemoreceptors have been identified inside the kidney, but their functional role is still largely unclear. The aim of this study was to investigate whether changes in urine output could modify the discharge rate of renal afferent fibers. Experiments were performed in anesthetized cats in which afferent renal nerve activity (ARNA) was recorded by standard electrophysiological techniques from a centrally cut renal nerve. Arterial pressure, renal blood flow velocity, urine flow rate, and renal pelvic pressure were also measured. Three diuretic maneuvers were tested in the same cat: intravenous administration of physiological saline (8 to 13 mL/min for 2 minutes), furosemide (1 mg/kg), and atrial natriuretic peptide (ANP, 1 μg/kg). The three maneuvers increased urine flow rate and pelvic pressure, respectively, 137.0±20.6% and 136.8±21.1% (saline), 148.6±31.7% and 139.6±43.5% (furosemide), and 75.9±7.9% and 62.1±21.2% (ANP) at the time of the maximum response. Arterial pressure slightly increased after saline, did not change after furosemide, and slightly decreased after ANP. Renal blood flow increased after saline and did not change after furosemide and ANP. The three maneuvers increased ARNA by 98.4±15.2% (saline), 270.7±100.8% (furosemide), and 59.6±23.4% (ANP). Changes in ARNA significantly correlate with changes in both pelvic pressure and urine flow rate. Our data demonstrate that increments in urine flow rate increase the firing rate of renal afferent fibers and suggest that (1) pelvic pressure is the major determinant of the neural response, and (2) this increased afferent discharge is due to activation of renal mechanoreceptors.