1. The role of the renal nerves in modulating the action of atrial natriuretic peptide (ANP) in the kidney was studied by comparing the responses to ANP in innervated and surgically denervated kidneys in anaesthetized rabbits. 2. A low dose of ANP (0.05 microgram/kg per min, i.v.) was used to minimize the confounding effects of systemic hypotension. 3. The natriuretic and diuretic responses to ANP were significantly greater in denervated kidneys than in kidneys with intact innervation. Sodium excretion from denervated kidneys rose by 7.49 +/- 3.11 mumol/min in response to ANP (approximately 55%, P < 0.05) compared to 0.84 +/- 0.59 mumol/min (approximately 28%, NS) in innervated kidneys. Urine flow increased markedly in denervated kidneys by 73.2 +/- 29.9 mumol/min (approximately 60%, P < 0.05) but not in innervated kidneys. 4. Fractional sodium excretion increased significantly in denervated kidneys in response to ANP (median 2.3% to median 3.0%, P < 0.05). 5. Renal blood flow, glomerular filtration rate (GFR) and glomerular capillary pressure were unchanged in response to ANP in either denervated or innervated kidneys. Pre-glomerular vascular resistance fell in denervated kidneys during ANP infusion. 6. The natriuresis and diuresis observed in the denervated kidneys, due to an increased fractional excretion of sodium without increases in GFR or glomerular capillary pressure, is consistent with effects of ANP on tubular reabsorption of sodium. 7. Thus, ANP produced a natriuresis and diuresis at a low dose in denervated but not in innervated kidneys. This indicates that reflex activation of renal nerves may antagonize the renal effects of ANP.