This study tests the possible influence of the urinary concentrating process and/or of vasopressin (AVP) on the progression of early chronic renal failure (CRF). Male Sprague-Dawley rats were submitted to 5/6 nephrectomy and were offered water ad libitum throughout the study. In addition, half of the rats (high water intake, HWI) received their food mixed with a water-rich agar gel. The other rats (normal water intake, NWI) ate the same amount of food plus agar in the usual dry powder form. This resulted in doubling the daily water ingestion in HWI. Renal function was studied for 10 wk and kidney morphology assessed thereafter. Increased water intake in HWI reduced solute-free water reabsorption and urine osmolality about threefold to 12 +/- 1 ml/day and 390 +/- 9 mosmol/kgH2O, respectively (week 5 as example). Hematocrit, plasma sodium, and plasma creatinine concentration were unchanged. The progressive increases in urinary protein excretion and in systolic blood pressure observed in this model of CRF were significantly slowed in HWI compared with NWI (at week 5, 8.6 +/- 1.8 vs. 23.1 +/- 6.2 mg protein/day and 142 +/- 8 vs. 167 +/- 10 mmHg, respectively). Remnant kidney weight per unit body weight was 21% lower in HWI than in NWI (P less than 0.02). Incidence of glomerulosclerosis was also reduced and was correlated with kidney weight (P less than 0.01). AVP plasma level (PAVP) and plasma renin activity (PRA) were measured in additional rats. PAVP was about twofold higher (P less than 0.05) and PRA twofold lower (P less than 0.001) in rats with 5/6 nephrectomy than in control rats with two kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)