Although it is known that hepatic failure occurs in late sepsis, it is not known whether there are alterations in hepatocellular function in early sepsis when hyperdynamic circulation exists in conjunction with hyperglycemia and hyperinsulinemia. To study this, indocyanine green (ICG) clearance and serum levels of hepatic enzymes were measured during early and late sepsis. Sepsis in rats was produced by cecal ligation and puncture (CLP). Ten hours following CLP (early sepsis) total hepatic blood flow (THBF) as measured by hydrogen polarography increased from 23.9 +/- 1.1 to 30.6 +/- 1.4 (ml/min/100 gm). ICG (5 mg/kg body weight--BW) was given intravenously and sequential blood samples taken to determine ICG clearance. ICG half-times (T/2) were 4.99 +/- 0.15 and 6.57 +/- 0.51 minutes for sham-operated and early sepsis rats, respectively (mean +/- S.E., P less than 0.01). SGOT and SGPT levels (IU/ml) increased from 38.1 +/- 0.6 to 69.8 +/- 2.6 and 9.9 +/- 0.4 to 25.6 +/- 1.5, respectively (P less than 0.001). Thus the T/2 of ICG as well as serum levels of liver enzymes increased significantly during early sepsis. Eight additional rats underwent CLP and were tested 16 hours later (late sepsis). THBF in late sepsis decreased to 15.5 +/- 0.5 ml/min/100 gm. ICG T/2 at that time was 8.2 +/- 0.48 min and SGOT and SGPT level were 132 +/- 14.5 and 42 +/- 3.4, respectively (P less than 0.001). These results indicate that heptocellular dysfunction occurs even in the early period of sepsis when THBF is increased. Progressive dysfunction occurs in late sepsis concomitant with a decrease in THBF.