BACKGROUND Adiponectin, an adipose-derived hormone with central and peripheral actions, is involved in the regulation of energy homeostasis. Interactions between genetic and environmental factors have been associated with decrease in circulating adiponectin leading to obesity. OBJECTIVE We investigated whether variants of the ADIPOQ gene encoding adiponectin interact with diet to predict serum adiponectin concentration. METHODS A cross-sectional study of healthy school-aged children of Greek origin (n = 991), aged 11.2 +/- 0.6 years was conducted in 2005-2006. DNA was genotyped for two SNPs [rs1501299 (n = 741) and rs17300539 (n = 713)] located in the ADIPOQ gene. Detailed dietary, behavioural, lifestyle, anthropometric and biochemical data were recorded for all participants. RESULTS Both SNPs were in HWE. The rs1501299 (GG vs GT + TT) x fibre interaction was significantly associated with adiponectin concentration (P = 0.028). When fibre intake was low, GG homozygotes exhibited significantly higher adiponectin concentrations compared to T allele carriers (mean +/- SD = 5.1 +/- 2.7 vs 4.2 +/- 2.3; P = 0.020). CONCLUSIONS In the present study, the rs1501299 x fibre interaction was significantly associated with adiponectin levels; in specific, GG homozygotes exhibited higher adiponectin levels compared to T carriers under conditions of lower fibre intake.