Male Mongolian gerbils (Meriones unguiculatus) were fed casein or soy protein in the presence and absence of dietary cholesterol for 15 months. Diets resembled the average North American diet in energy contributions from protein, fat and carbohydrate, cholesterol content and fatty acid profile. At month 0, 3, 6, 9, 12 and 15, plasma samples were analyzed for total cholesterol (TC), HDL cholesterol (HDLC) and triglyceride (TG) concentrations. Plasma LDL cholesterol (LDLC) was estimated indirectly. Liver TC was also determined at these time points. Comparisons of protein source and cholesterol level were averaged over the 15 month period. Casein-fed gerbils had significantly higher plasma TC and TG levels and lower HDLC levels (as a percent of TC) compared to soy-fed animals, independent of the presence or absence of dietary cholesterol. LDLC was significantly elevated in casein-fed gerbils only when cholesterol was present in the diet. Elevations in plasma TC levels were reflected by elevations in liver TC. Despite plasma lipid elevations that are consistent with the development of atherosclerosis (AS) and coronary heart disease (CHD) in humans, hyperlipidemic gerbils do not develop AS. Further characterization of gerbil lipid metabolism responses to dietary alterations aimed at the prevention of CHD in humans is necessary to elucidate the mechanism for the gerbil's resistance to AS.