In screening for effective additives for the long-term culture of hepatocytes, the hepatoprotective effect of alpha(1)-acid glycoprotein (AGP) was observed. AGP prevented primary hepatocytes from undergoing cell death induced by the chemical toxin, bromobenzene. Moreover, AGP added to medium was found to maintain the number of viable hepatocytes for as long as 6 d. The hepatoprotective effect of AGP was lost by removing sialic acid groups at the N-glycan chain terminal of AGP. It is shown that the complete form of N-glycan chain is needed for the hepatoprotectivity of AGP.