To determine the relationship between plasma immunoreactive atrial natriuretic peptide (i-ANP) and renin-angiotensin-aldosterone system (RAAS), plasma i-ANP, plasma renin activity (PRA) and plasma aldosterone (PA) were assayed in 29 patients (19 hypertensive and 10 normotensive) with chronic renal failure (CRF), and in 10 healthy subjects. Hypertensive patients had higher i-ANP values than normotensive patients and controls (P less than 0.05 and P less than 0.01 respectively). There was no significant correlation between plasma i-ANP and creatinine concentrations in hypertensive patients, whereas this correlation was statistically significant in normotensive patients (r = 0.70, P less than 0.01). Other positive correlations were between plasma i-ANP and systolic blood pressure in hypertensive patients (r = 0.69, P less than 0.01) and between plasma ANP and mean arterial pressure in normotensive patients (r = 0.63, P less than 0.01). There was significant negative correlation between plasma ANP and fractional sodium excretion (FENa) in hypertensive patients (r = -0.47, P less than 0.05), though there was significant positive correlation in normotensive patients (r = 0.80, P less than 0.01). Hypertensive patients, with the exception of one anuric patient and another with atrial fibrillation, had a significant negative correlation between FENa and systolic arterial blood pressure (r = 0.64, P less than 0.01). The patient group had increased PRA and PA values (P less than 0.01 and P less than 0.001 respectively) and showed positive correlation with mean arterial pressure (MAP) (r = 0.71, P less than 0.001 and r = 0.58, P less than 0.01 respectively). These results show that increased concentrations of immunoreactive ANP circulate in CRF together with activated RAAS. We demonstrate that elevated ANP cannot affect blood pressure and natriuresis in hypertensive patients with CRF, whose RAAS is activated.