The beta2-adrenoceptor gene may be of particular importance for human obesity because catecholamines have a central role in energy expenditure both as neurotransmitters and hormones. The gene is highly polymorphic, and individual polymorphisms have previously been examined for their relationship to obesity, but results are conflicting. We performed a haplotype analysis of the beta2-adrenoceptor gene in 1354 women and 421 men, all healthy and at least second generation Scandinavian and with a large interindividual variation in body fat mass. We found three common haplotypes. One of these haplotypes, identified as T, A, C, C at nucleotide positions -47, 46, 79, and 491, was in its homozygote form more common among lean (18%) than obese (13%) women (p = 0.0028), but there was no association with obesity in men (p = 0.47). Women who were homozygous for this haplotype had lower BMI (p = 0.009) and percentage body fat (p = 0.005) in comparison with those having other haplotypes or being heterozygous for TACC. The data suggest an important role of the beta2-adrenoceptor gene in obesity because a common haplotype has recessive protective effects against excess body fat, at least in women.