To date, no studies have compared the effects of consuming a low-fat diet and a high monounsaturated fatty acid (MUFA) diet, under unrestricted energy intake conditions, on plasma C-reactive protein (CRP) concentrations. Men [n = 61; 37.5 +/- 11.5 y old (mean +/- SD), mean BMI 29.0 +/- 5.0 kg/m2] were randomly assigned to consume ad libitum a moderately low-fat diet (25.8% of energy intake from fat) or a high-fat diet rich in MUFA (40.1% of energy intake from fat, 22.5% from MUFA) for 6-7 wk. Plasma CRP concentrations were measured using a highly sensitive assay. Neither diet affected the plasma CRP concentration. However, baseline CRP concentrations predicted lipoprotein/lipid responsiveness to the experimental diets. After intake of the low-fat diet, plasma total and VLDL-triglyceride (TG) concentrations were increased in the subgroup with high CRP concentrations (P < 0.05 and P < 0.01, respectively) whereas they were reduced in the subgroup with low CRP concentrations at baseline (P < 0.01 for both). The high-MUFA diet reduced plasma TG, VLDL-TG, and VLDL cholesterol only in the subgroup with low CRP at baseline (P < 0.0001). In conclusion, the low-fat diet and the high-MUFA diet did not affect plasma CRP concentrations. However, baseline plasma CRP concentrations may modulate the diet-induced changes in plasma lipid and lipoprotein concentrations.