The effect of dietary protein source on the kinetics of plasma very low-density lipoprotein (VLDL) (Sf 60 to 400) in hypercholesterolemic men was investigated. Using a crossover design, five subjects received sequentially either 1) a high polyunsaturated fat, low cholesterol control diet containing mixed protein from meat, dairy products, and plant sources or 2) an all-plant protein experimental diet in which the meat and dairy protein of the former diet was replaced by soybean protein and soy milk. There was no significant change in the mean values for fasting serum cholesterol and triglycerides over the 6-wk period of administration of the control versus experimental diets. The kinetics of VLDL (Sf 60 to 400) apolipoprotein B were studied at the end of each dietary period after reinjection of 125I-labeled autologous VLDL (Sf 60 to 400). The VLDL apolipoprotein B pool size was similar during the experimental and control protocols; however, the fractional catabolic rate was consistently higher during the experimental protocol (8.5 +/- 1.3 versus 6.5 +/- 1.2 day-1, p less than 0.01) and the production rate of apoprotein B was higher than control in four of five subjects (mean values 18.6 +/- 3 versus 12.6 +/- 1 mg/day/kg, respectively). Administration of an all-plant protein diet significantly increased the fractional turnover rate of VLDL apolipoprotein B, even when no changes in VLDL ago B pool size or VLDL lipid concentrations were observed.