Urea synthesis is an exclusive biosynthetic function of the liver. Since the exact relationship between urea synthesis in vivo and functional liver mass remains unclear, we established an animal model using oral protein loading and measurement of resultant urea synthesis in rats. We studied rats subjected to sham operation, 40% hepatectomy, 66% hepatectomy, portacaval shunt and CCl4-induced cirrhosis. Urea synthesis was calculated as the sum of urinary urea excretion and accumulation of urea in body water during the 6-hr period after oral administration of a casein protein load equivalent to 20 gm per kg body weight. Peak urea synthesis rate in the sham-operated group of rats was 142 +/- 11 mumoles per hr per gm wet liver weight (mean +/- 1 S.D.), 473 +/- 34 mumoles per hr per gm liver protein and 80 +/- 5 mumoles per hr per mg liver DNA. This rate closely matched those of the other groups for each type of liver mass measurement. Marked reduction (p less than 0.01) of urea synthesis on a DNA basis was noted only in the CCl4-cirrhotic livers, related to the significantly higher (p less than 0.01) DNA content of the cirrhotic livers. Similarly, increased (p less than 0.05) liver protein content of the sham-operated rats when compared with the other groups was reflected in slightly lower urea synthesis rates expressed on the basis of liver protein (p less than 0.05) when compared to that of all other groups.(ABSTRACT TRUNCATED AT 250 WORDS)