The effects of low/high fat diets and simple/complex carbohydrate intake on specific aspects of plasma VLDL and LDL metabolism were evaluated. Guinea pigs were fed for 4 wk two different fat/carbohydrate concentrations: 2.5/58 (g/100 g) or 25/29 (g/100 g) with either sucrose or cornstarch as the sole carbohydrate source. Intake of high fat diets resulted in higher plasma cholesterol (P < 0.001), whereas sucrose intake resulted in higher plasma triacyglycerol (TAG) concentrations (P < 0.03). Intake of starch increased apolipoprotein (apo) B secretion rates (P < 0.001), and nascent VLDL were smaller and contained less TAG/apo B than particles from the sucrose-fed group (P < 0.01). Guinea pigs fed the starch diets had higher plasma VLDL apo B flux and faster VLDL apo B clearance than those fed sucrose diets (P < 0.01). In addition, more rapid VLDL removal from plasma in guinea pigs fed complex carbohydrate/high fat diets was associated with less conversion of VLDL to LDL and lower plasma cholesterol concentrations compared with the high fat/sucrose group (P < 0.01). Low fat compared with high fat intake resulted in 60% more rapid plasma LDL apo B fractional catabolic rates (FCR). The LDL apo B fractional catabolic rate of all dietary groups was inversely correlated with plasma cholesterol concentrations (r = -0.83, P < 0.001). These results demonstrate that in guinea pigs, low fat diets decrease plasma LDL cholesterol concentrations by increasing LDL turnover rates, and complex carbohydrates reduce plasma TAG by affecting the composition of nascent VLDL particles and by increasing VLDL apo B catabolism.