This study examined the effect a polymorphism (L162V) in the gene for peroxisome proliferator activated receptor (PPAR) alpha in the development of non-insulin-dependent diabetes mellitus (type 2 DM), obesity and hyperlipidaemia. The frequency of the L162V polymorphism in the PPARalpha gene was determined in 370 morbidly obese patients who underwent gastric banding surgery, 154 patients attending a type 2 DM clinic, 188 patients attending a lipid clinic and 199 healthy blood donors. The overall frequency of the V allele of the L162V polymorphism was 0.06. There were no significant differences in the allele frequency between patients with morbid obesity, hyperlipidaemia, type 2 DM and healthy controls, suggesting that it does not play a major role in the development of these conditions. The polymorphism was associated with a lower body mass index (BMI) in two independently recruited groups of patients with type 2 DM. There was no effect of the polymorphism on subjects without type 2 DM. Thus a polymorphism in PPARalpha protects type 2 DM patients from the overweight which is frequently associated with their condition.