The remnant kidney model of progressive renal failure in the rat was used to assess the relationships between the renin-angiotensin system, exchangeable body sodium, and both plasma concentration and atrial content of atrial natriuretic factor (ANF) measured sequentially over 4 weeks. Following subtotal nephrectomy plasma creatinine (mumol/L) rose from 40 +/- 6 (sham) to 107 +/- 24 (P less than 0.05) at 1 week, and rose further to 124 +/- 20 (P less than 0.05) by 4 weeks. Plasma renin activity (nanograms of angiotensin I/mL/min) rose from 4.5 +/- 0.5 to 11.8 +/- 2.8 (P less than 0.05) at 1 week, but was suppressed by 4 weeks to 2.2 +/- 0.3 (P less than 0.001). Plasma angiotensin II (pg/mL) was 52 +/- 2 (sham), 117 +/- 20 at 1 week (P less than 0.05) and 51.3 at 4 weeks. Exchangeable sodium (mmol/kg) rose progressively from 43.2 +/- 5 (before surgery) to 48.6 +/- 0.9 at 1 week and 50.8 +/- 2.2 at 4 weeks. Plasma atrial natriuretic factor (ANF) (pg/mL) rose progressively from 114 +/- 6 (sham) to 248 +/- 31 (P less than 0.01) at 1 week and 456 +/- 78 at 4 weeks (P less than 0.01). Atrial ANF content fell as the plasma concentration rose. In the remnant kidney model of progressive renal failure there was a progressive increase in exchangeable body sodium and plasma atrial natriuretic factor, with reciprocal changes in atrial ANF content suggesting that ANF secretion rate was increased. Initially the renin-angiotensin system was stimulated, but later it was suppressed.