Genetic factors, alone or in interaction with components of the diet, are thought to be involved in the development of the metabolic syndrome. The objective of our study was first to compare the frequency of the peroxisome proliferator-activated receptor (PPAR) α-L162V polymorphism in a sample of men with and without the metabolic syndrome as defined by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) guidelines, and secondly, to evaluate gene–diet interaction effects on features of the metabolic syndrome. The PPARα-L162V genotype was determined in a sample of 632 men by a polymerase chain reaction–restriction length polymorphism (PCR–RFLP)-based method; fat as well as saturated fat intakes were evaluated by a dietitian-administered food frequency questionnaire. The frequency of the V162 allele was similar in men with (n= 281) and without (n= 351) the metabolic syndrome (χ 2= 0.03, p= 0.84) but was higher in subjects having simultaneously abdominal obesity, hypertriglyceridemia, and low high-density lipoprotein cholesterol (HDL-C) levels (χ 2= 3.73, p= 0.05). Carriers of the V162 were characterized by higher plasma apolipoprotein B and triglyceride (TG) levels (p= 0.10, p= 0.004). In a model including the PPARα-L162V polymorphism, fat or saturated fat, its interaction, and covariates (smoking habits, and energy and alcohol intake), the interaction explained a significant percentage of the variance observed in waist circumference (p< 0.05). In conclusion, the PPARα-L162V polymorphism alone or in interaction with dietary fat intake is associated with components of the metabolic syndrome.