Serotonin has been related to feeding behaviour and body weight control through its suppressive effect on appetite. Conflicting results have been published in the literature regarding the association between the - 1438 G/A promoter polymorphism of the 5HT2A gene with obesity-related variables. The aim of this study was to assess the association between the--1438 G/A polymorphism of the 5HT2A gene with childhood obesity in a Spanish population. A total of 136 cases aged 6-16 years with BMI above the 97th percentile of the Spanish BMI reference data for age and gender were matched by gender and age (+/- 6 months) with 136 controls. Additionally, 43 obese children and their parents were selected for a family-based association study (case-parent study). Genotyping was carried out by polymerase chain reaction and restriction enzyme analysis. Conditional logistic regression and transmission/disequilibrium test were used to assess genotype-obesity association. In the matched case-control study, the crude and adjusted odds ratios for the association between 5HT2A--1438 G/A genotypes were nonsignificant. Likewise, no association is suggested by the case-parent study. In conclusion, it is unlikely that the--1438 G/A polymorphism of 5HT2A gene may influence obesity in a Spanish children population.