The protein synthesizing capacity of liver parenchymal cells isolated from 3-, 12-, 24-, 31- and 36-month-old rats was determined by the incorporation of 14C-leucine. Conditions for optimum protein synthesis included the use of an enriched medium (modified Waymouth's MB 752/1) and cell suspension concentrations ranging from 0.25 to 4 X 10(6) cells/ml medium. The cells were incubated with a dose of 6 micronmol leucine/ml medium for 2 h at 37 degrees C under an atmosphere of 95% O2 and 5% CO2. With parenchymal cells isolated from 3-month-old rats, a leucine incorporation rate of 14.4 nmol leucine/h/10(6) cells was found. The capacity of the parenchymal cells to synthesize protein decreased between 3 and 12 months, remained constant between 12 and 24 months and increased between 24 and 26 months. Degradation of newly synthesized proteins or reutilization of 14C-leucine did not occur during the incubation period. The ratio between albumin and total protein synthesis as a function of age was determined. This ratio did not change between 3 and 24 months but there was a significant increase between 24 and 36 months. The increase in total protein synthesis in late age may be due to a compensation by the liver for a more pronounced proteinuria, increased proteolysis or an accumulation of "altered" proteins.