To examine the effect of malnutrition on liver protein metabolism and synthesis during liver regeneration, 104 rats were allocated to semi-starvation or ordinary food intake for 1 week. Half of each group was sham operated and the other half was partially hepatectomized. Specimens were taken from the liver at the time of liver resection and from animals killed 24, 48 and 72 h after the primary operation. Liver samples were analysed for DNA and protein, and in the 48-h groups RNA and protein synthesis were also analysed. Protein synthesis was measured by the flooding method using L[4-3H] phenylalanine. The liver weight during regeneration increased very rapidly in the well-nourished animals, but when expressed as percent of body weight or as proportional increases, the difference between well-nourished and malnourished animals disappeared. The fractional rate of protein synthesis was not changed in sham-operated malnourished or well-nourished animals. During regeneration, protein synthesis in well-nourished animals was elevated compared to sham-operated controls, but a lesser stimulation was seen in malnourished rats. It was concluded that the mechanism of liver regeneration depends on nutritional state, involving an increase in protein synthesis in well-nourished animals, but relying more on a decrease in protein degradation or cessation of secretory protein synthesis in malnourished animals.