The effect of dietary casein and soy protein on lipoprotein metabolism was compared in the Golden Syrian hamster (Mesocricetus auratus). Total plasma cholesterol was similar in animals fed either protein, but significant differences were seen in lipoprotein profile. In animals fed soy protein, cholesterol concentrations were lower in very-low-density lipoproteins (VLDL) but higher in low-density and high-density lipoproteins, compared with those fed casein. Significant differences were also seen depending on the nutritional state of the animals. In casein-fed hamsters, total plasma triacylglycerol and chylomicron + VLDL cholesterol and triacylglycerol were significantly higher when blood was collected during feeding, compared with animals that had been fasted overnight. By contrast, no significant change was seen in animals on the soy protein diet. This suggests that either intestinally derived lipoproteins are more rapidly cleared on the soy protein diet or that soy inhibits feeding-induced VLDL secretion. Fecal bile acid excretion was higher in the soy protein group, and there was a significant correlation between soy intake and bile acid excretion. Hepatic cholesterol decreased as the amount of soy protein consumed increased, suggesting that it is this pool of cholesterol that is used to replace the excreted bile acids. No significant difference was seen in plasma insulin or glucagon between hamsters fed the two proteins. Plasma triiodothyronine concentrations were, however, significantly higher and thyroxine concentrations lower in the soy protein-fed animals. This study shows specific effects of dietary proteins on plasma lipoprotein concentrations dependent on nutritional status of the animal.