Galactose clearance kinetics at plasma concentrations of 0.01-0.1 mg/ml were studied during continuous infusion of 25-100 mg D-galactose per minute. In 10 subjects, plasma galactose vs. time curves during 140-min infusion, and 60 min thereafter, showed the data to fit a single-compartment model and attain 95% of plasma steady state by 80 min. Doubling the infusion rate in 14 subjects resulted in an 8% reduction in clearance at the higher rate. Hepatic extraction in normal subjects was 94%, while in cirrhotics it was 79%. Day-to-day reproducibility in 11 subjects gave a coefficient of variation of 4.5%. Extrahepatic clearance showed 2% of the total to occur in the urine, and 2.3% to occur by erythrocyte metabolism. The overall mean (+/-SD) clearance in the normal subjects of 1378 +/- 218 ml/min was significantly (p less than 0.05) greater than for the stable cirrhotics at 918 +/- 279 ml/min, but not significantly different from patients with acute hepatocellular damage at 1186 +/- 300 ml/min. This index gives flow-dependent hepatic clearance, and provides a noninvasive measure of effective liver blood flow.