Twelve patients with recently diagnosed acute viral hepatitis underwent serial 99mTc-galactosyl neoglycoalbumin scanning of the liver (for up to 8 mo). Injection of 99mTc-galactosyl neoglycoalbumin (150 mBq) at a rate of 3.5 mg (50 nmol; 1 ml) revealed that the liver is the exclusive site of tracer uptake. Simulation of 99mTc-galactosyl neoglycoalbumin kinetics allowed quantification of galactosyl neoglycoalbumin binding to human hepatic binding protein. Return of liver function test scores to normal values was associated in two patients with hepatitis A, in four patients with hepatitis B and in two patients with non-A, non-B hepatitis virus infection, with increases in hepatic binding protein concentration (up to three times the initial concentration), binding rate constant and hepatic blood flow. In the other four patients (three patients with hepatitis B and one patient with cytomegalovirus infection) a prolonged course of disease was monitored. In the mean, hepatic binding protein increased from 0.41 +/- 0.11 mumol/L after onset of acute hepatitis (n = 12) to 0.78 +/- 0.21 mumol/L after 6 mo of follow-up (n = 10) (p less than 0.001). During this period, binding rate constant (72.4 +/- 12.6 vs. 82 +/- 11.5 mumol/L/sec; p less than 0.05) and hepatic blood flow (0.027 +/- 0.0051 vs. 0.031 +/- 0.0083 L/sec; p less than 0.05) increased. Hepatic binding protein concentration correlated highly with actual laboratory test results for liver function (r = 0.98; p = 0.0001). We conclude that scintigraphic evaluation of functional liver cell mass using the new receptor-tracer 99mTc-galactosyl neoglycoalbumin could provide an in vivo diagnostic means of quantifying liver function and assessing liver morphology. In addition, our findings suggest that changes in hepatic binding protein-receptor concentration are likely to occur in vivo.