Previous studies suggest that hypoxia and hypercapnic acidosis exert a renal nerve mediated adverse effect on renal haemodynamic function. We therefore examined the effect of hypoxia and hypercapnic acidosis on renal blood flow and glomerular filtration rate responses to lowering renal perfusion pressure from 125 to 75 mmHg in the anaesthetized dog. To study the role of renal nerves in these responses, paired innervated and denervated kidneys were studied in each animal. Hypoxia (PO2 43 +/- 3 mmHg) affected neither renal blood flow nor glomerular filtration rate responses to decreasing renal perfusion pressure. Hypercapnic acidosis (PCO2 71 +/- 2 mmHg; pH 7.03 +/- 0.01) significantly decreased both renal blood flow and glomerular filtration rate as renal perfusion pressure was lowered. This effect of hypercapnic acidosis could be abolished by renal denervation. These findings suggest that hypercapnic acidosis results in renal nerve stimulation, which prevents the usual decrease in renal afferent arteriolar tone that occurs in response to lowering of renal perfusion pressure.