Three patients with cirrhosis, ascites, and dilutional hyponatremia were treated with demeclocycline in an attempt to correct the abnormal water retention. Demeclocycline administration (600 to 900 mg/day for 8 to 9 days) resulted in [a] increased blood urea nitrogen and plasma creatinine concentrations; [b] reduction of the inulin clearance by between 63% to 78% and of paraaminophippurate clearance by 36% to 77%; and [c] an impairment of the renal concentrating ability. Urine osmolality decreased to hypotonic levels, but polyuria did not appear, probably because it was prevented by the reduction of the glomerular filtration rate. Renal failure was reversible on withdrawal of demeclocycline. No other causes than demeclocycline administration could be found to explain the reduction of the glomerular filtration rate and the estimated renal plasma flow.