This study investigated the effects of long-term chloroquine and ethanol administration on renal fluid and electrolyte handling and kidney structure. Male Sprague-Dawley rats were orally administered with chloroquine diphosphate (20 microg kg(-1) bw) and/or ethanol (1.6 g kg(-1) bw) every third consecutive day for 4 weeks. Urine volume and total urinary outputs of Na+ and K+ were determined from 24-h samples. For detailed renal studies, rats were subsequently anaesthetised and challenged with a continuous jugular infusion of 0.077 M NaCl at 150 microl min(-1) 24 h after the last treatment. After a 3-h equilibration period, urine flow, Na+ and K+ excretion rates were determined over a 4-h period. Plasma concentrations of AVP and aldosterone were measured in unanaesthetised rats and in anaesthetised rats after hypotonic saline infusion. In separate groups, the rats were anaesthetised with an overdose of ether after 4 weeks of treatment and part of the right kidney was quickly collected and routinely processed for light microscopy. Chloroquine decreased Na+ excretion and increased plasma aldosterone concentrations in anaesthetised rats. Ethanol alone did not alter urinary Na+ outputs or aldosterone levels. Combined chloroquine and ethanol increased renal Na+ excretion, but did not affect plasma aldosterone levels. In unanaesthetised animals all treatments increased aldosterone levels by comparison with control rats. Urinary Na+ excretion was decreased by separate administration of either chloroquine or ethanol, but increased by combined treatment. Microscopic studies showed that concurrent chloroquine and ethanol administration induced extensive damage of the proximal tubule and collecting ducts cells. The results of this study suggest that alcohol consumption and chloroquine administration could result in diminished renal function possibly due to alteration of renally active hormones or kidney morphology.