Experiments were designed to determine whether substance(s) other than electrolytes might activate tubuloglomerular feedback in experimental fulminant hepatic failure. Severe hepatic damage and renal dysfunction were induced by intravenous administration of D-galactosamine. Sera from normal or D-galactosamine-treated rabbits were dialyzed against glucose solution to reduce electrolyte concentrations. Tubuloglomerular feedback response was evaluated in rat nephrons by measuring the early proximal flow rate (EPFR) during orthograde perfusion of the loop of Henle. EPFR was reduced by 28 and 48% with Ringer’s solution and sera from D-galactosamine-treated rabbits, respectively, but was not altered by normal sera. Substance(s) other than electrolytes in the sera from D-galactosamine-treated rabbits might activate the tubuloglomerular feedback to reduce glomerular filtratio