OBJECTIVE: To determine if fat deposition within mid-thigh muscle, represented by low density lean tissue density, is associated with age, low physical fitness, hyperleptinemia, hyperinsulinemia and dyslipidemia in women. SUBJECTS: Seventy-two women aged 18–69 y with a wide range of total body fat (10–55%) and maximal aerobic capacity (VO2max: 17–61 ml/kg−1/min−1). MEASUREMENTS: Mid-thigh muscle, mid-thigh fat, low density lean tissue, intra-abdominal adipose tissue (IAAT) and subcutaneous abdominal fat (by computed tomography, CT), fat mass (FM) and fat-free mass (FFM) (by dual energy x-ray absorptiometry, DEXA), plasma insulin and leptin (by radioimmunoassay, RIA) and lipoprotein lipid profiles (by enzymatic methods). RESULTS: VO2max declined with age (r0.59, Pr=0.68, r=0.57, r=0.63,Pr=0.52), VO2max (r=0.56), FFM (r=0.35), fat mass (r=0.68), IAAT (r=0.66) and subcutaneous abdominal fat (r=0.67, all, Pr=0.44, 0.34, 0.41, 0.50, 0.53, respectively, all PP<0.05). CONCLUSIONS: Mid-thigh low density lean tissue is directly related to age and adiposity. Furthermore, it appears that fat accretion in skeletal muscle adversely influences plasma insulin and lipoprotein metabolism in women, but not independently of total adiposity and age.