We investigated whether amino acid substitution of tryptophan by arginine at the residue 64 (64 Arg) of beta 3-adrenergic receptor affects on the degree of reduction in the abdominal fat distribution during a 3-month weight reduction program in either pre- or postmenopausal Japanese women. Beta 3-adrenergic receptor gene polymorphism was examined in 90 Japanese obese women by restriction-enzyme cleavage conformation. The visceral and subcutaneous fat area was measured by magnetic resonance imaging. The baseline body mass index, body weight, fat mass and abdominal subcutaneous and total fat area in 15 obese postmenopausal women with a beta 3-adrenergic receptor (64 Arg) were significantly higher than those in 25 postmenopausal obese women with a beta 3-adrenergic receptor (64 Trp/64 Trp). In contrast, no such differences were found in the 50 premenopausal obese women. After a 3-month weight reduction period, the ratio of visceral to subcutaneous fat areas tended to be lower in both pre-and post-menopausal women with a beta 3-adrenergic receptor (64 Arg), but statistically significant in only the premenopausal obese women (p<0.05). The absolute changes in visceral fat areas in 5 homozygotes with a beta 3-adrenegic receptor (64 Arg/64 Arg) was significantly smaller than those in 50 obese women with a beta 3-adrenegic receptor (64 Trp/64 Trp). These results thus suggest that an amino acid substitution at residue 64 of beta 3-adrenergic receptor may play an important role in the regulation of fat distribution in Japanese obese women. (C) 1999 Elsevier Science Inc.