OBJECTIVE: To investigate the association of a polymorphism at position 294 (+294T/C) in the Peroxisome Proliferator-activated Receptor delta (PPARdelta) with body mass index (BMI) and the additional role of a gene-to-gene interaction between PPARdelta, PPARalpha and PPARgamma. DESIGN: An association between genetic variations in PPARdelta, PPARalpha and PPARgamma and indices of obesity and metabolism. SUBJECTS: A group of 462 moderately obese (mean BMI 28.9+/-7.7) and dyslipidemic, middle-aged (mean age 43.9+/-13.7), Caucasion men and women.Measurements:The three most frequent single-nucleotide-polymorphisms (snp) in PPARdelta (+294T/C), PPARalpha (L162V) and PPARgamma (P12A) were genotyped and associated with clinical parameters.Results:The C allele in PPARdelta was significantly associated with a lower body mass index. Moreover an interaction between the polymorphisms in PPARalpha and PPARdelta on body weight could be demonstrated. CONCLUSION: Our data provide further evidence for an involvement of PPARdelta in the regulation of BMI.