The metabolism of subcutaneous abdominal and femoral fat cells was studied in postmenopausal women and matched men of similar age and weight index. Lipoprotein lipase (LPL) activity was similar in both regions in the postmenopausal women. However, a group of women who underwent treatment with estrogen and progestins had considerably higher LPL activity in the femoral cells. Testosterone treatment for 7 days did not change LPL in either region in middle-aged men. Femoral adipocytes from both men and postmenopausal women were markedly unresponsive to catecholamine in comparison with abdominal cells. No clear effect of the sex hormones was seen on lipolysis in the women. Treating men with testosterone increased basal lipolysis in the abdominal cells. Abdominal fat cells were more responsive to the antilipolytic effect of insulin. Both responsiveness and sensitivity to insulin were somewhat greater in the abdominal fat cells from men (ED50 approximately 0.02 nm) than from women (ED50 approximately 0.17 nm). Insulin binding, however, was similar in fat cells from the abdominal and the femoral regions when the results were expressed per unit surface area. Thus, regional differences in fat cell metabolism are seen in both postmenopausal women and elderly men. LPL activity in the femoral region seems to be under the control of female sex hormones while lipolysis appears to be less influenced by sex hormones.