In this article we examine the production of very low-density lipoprotein (VLDL) by perfused livers obtained from chow- and cholesterol-fed nonhuman primates. These data illustrate two important features of VLDL production. First, VLDL is secreted from the liver in a form very close to that of its plasma counterpart. Thus for chow-fed animals, plasma VLDL and liver perfusate VLDL have similar lipid compositions. Second, the composition of VLDL can be modified significantly by diet in each of two primate species, the Rhesus monkey and the baboon. Rhesus monkey livers uniformly secrete larger quantities of VLDL and show more dramatic dietary effects than do baboon livers. Nevertheless, perfused livers from both species reveal qualitatively similar responses to dietary peanut oil and to lard fed in combination with cholesterol. Both fat-containing diets induce the livers to secrete VLDL enriched in cholesteryl ester compared with control perfusates yet still cholesteryl ester deficient compared with the animals' plasma VLDL. Peanut oil diet reduces the hepatic output of VLDL-associated apoprotein B and triglyceride, whereas lard increases hepatic secretion of VLDL-associated lipids and apoprotein E. We conclude that the nature of dietary fat plays an important role in determining the profile and composition of lipoproteins formed and secreted by the primate liver. We have also briefly reviewed the production of high-density lipoprotein, which is probably formed in the plasma from many sources, with special emphasis on the possible role of newly secreted lipid-poor apolipoprotein A-I and A-II.