Several studies have reported that carriers of the 103I allele of the melanocortin-4 receptor (MC4R) gene had lower body weight than did persons with the wild-type genotype. A recent study found an association of the MC4R 103I variant with carbohydrate intake, which may mediate some of the association of this variant with leanness. OBJECTIVE: The purpose of the study was to investigate the association between the MC4R V103I polymorphism and the dietary intake of persons with severe obesity, which was derived by using the Willett food-frequency questionnaire. DESIGN: The MC4R V103I polymorphism was genotyped in a group of 1029 severely obese white subjects with an average body mass index (BMI; in kg/m(2)) of 46.0 (range: 33-92). RESULTS: Carriers of the 103I allele had significantly higher daily energy (364 kcal/d or 19%; P = 0.03) and carbohydrate (57 g/d or 27%; P = 0.01) intakes than did noncarriers, but there was no relation with BMI. No notable association of this polymorphism with lipid and glucose variables of the metabolic syndrome was observed. CONCLUSIONS: The higher dietary intake of carbohydrates in severely obese persons with the MC4R 103I variant is in line with previous findings. It may indicate a differential effect on body size measures in extremely obese subjects as compared with the general population.