OBJECTIVES: To estimate the heritabilities of maximally attained lung function in young adult twins, and to examine whether circulating leptin, leptin (LEP) and leptin receptor (LEPR) gene polymorphisms are associated with maximally attained lung function. METHODS: Measures on forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) were available of 578 twins recruited from the East Flanders Prospective Twin Survey (165 monozygotic (MZ) and 73 dizygotic (DZ) complete pairs and 102 single twins). Twin model fitting and (genetic) association analyses were performed. RESULTS: Intra-pair correlations of FEV(1) and FVC did not differ significantly between MZ monochorionic and MZ dichorionic pairs. Heritability estimates of FEV(1) and FVC were 69% and 63%, respectively. The A allele of the LEP 19G>A SNP was significantly associated with a lower FEV(1) (p(Additive) = 0.01) and FVC (p(Dominant) = 0.047), while the LEPR K109R and Q223R SNPs showed no associations. Accounting for body mass index, serum leptin was negatively associated with FVC (p = 0.02) in men, but not in women. CONCLUSIONS: More than 60% of variation in maximally attained FEV(1) and FVC is explained by genetic factors. Moreover, these results suggest that leptin may be important in the determination of maximally attainable lung function.