OBJECTIVE: A matched case-control study was conducted in a population of Spanish children and adolescents (5-18 years old), to assess the interaction between the Gln27Glu polymorphism of the ADRB2 and television (TV) watching on obesity risk. PATIENTS: Obese (n=165) and control subjects (n=165) matched by sex and age were recruited and classified according to Spanish reference data. Results. Using conditional logistic regression, we calculated the obesity risk linked to the polymorphism. A statistically significant association was found for 27Glu carrier allele girls (OR = 1.95; 95% CI = 1.02-3.70), but no association was apparent among boys. In the fully adjusted model, the odds ratio for obesity linked to the genotype Glu27Glu in the female population rose to 4.84 (95% CI = 1.37-17.10). Moreover, we found a significant negative interaction between hours of TV watching and the Gln27Glu polymorphism for obesity risk in girls. Surprisingly, among 27Glu carrier subjects, even girls with a low level of TV watching ( < 12.5 h/week) had a high obesity risk (OR = 4.60; 95% CI = 1.01-20.02), which was not very different to the odds ratio values for sedentary girls carrying the 27 Glu allele watching TV more than 12.5 h/week (OR = 6.05; 95% CI = 1.31-27.71). Conclusion. A higher risk of obesity was found for girls carrying the 27Glu allele of the ADRB2 gene even when they spent less than 12.5 h/week watching TV. In addition, our results suggest that the effect of sedentary lifestyle on obesity risk may depend on the genotype of the subject.