The effects of sympathetic- and parasympathetic-nerve stimulation on the synthesis of transferrin and other serum proteins from [14C]leucine and their secretion were studied in rat liver perfused in situ. The radioactivities incorporated into perfusate transferrin, albumin and total protein increased with time during 90 min perfusion after an initial lag period of 15-30 min. The increases in the radioactivities of the perfusate proteins were inhibited by electrical stimulation of the hepatic nerve, whereas the increases were enhanced by vagal-nerve stimulation. Measurement of the incorporation of [14C]leucine into transferrin in the microsomal and cytosol fractions of the liver after 90 min perfusion revealed that the synthesis of this serum protein was suppressed by hepatic-nerve stimulation and increased by vagal-nerve stimulation. The results indicate that the biosynthesis and secretion of transferrin, and possibly other serum proteins, are inhibited by sympathetic-nerve stimulation and enhanced by parasympathetic-nerve stimulation.