The heritability of trabecular volumetric bone mineral density (BMD) determined by quantitative computed tomography (QCT) has not yet been reported. The purpose of this study was to investigate the heritability of BMD as determined by QCT and DXA in 124 women and 120 men (age 39-83 years, BMI 17-75, 84% type 2 diabetics) from 101 families (232 sibling pairs) in the Diabetes Heart Study. Volumetric BMD had a heritability (h2) estimate of 0.73 (SE = 0.15, P < 0.0001) at the lumbar spine and 0.71 (SE = 0.15, P < 0.0001) at the thoracic spine. Areal BMD heritability estimates were 0.56 for PA spine, 0.43 for total hip, 0.43 for femoral neck, 0.45 for distal radius, 0.42 for mid-radius, and 0.52 for whole body (all P < 0.01). After accounting for familial correlation using generalized estimating equations, volumetric BMD was inversely associated with age (r = -0.52, P < 0.0001) and duration of diabetes (r = -0.24, P < 0.01) and positively associated with body weight (r = 0.25, P < 0.01). In multivariate analysis, adjustment for age, sex, and race lowered the h2 estimates for volumetric BMD at the lumbar (h2 = 0.41, P < 0.01) and thoracic (h2 = 0.48, P < 0.001) spine, increased the h2 estimate for areal BMD at the mid radius (h2 = 0.58, P < 0.0001), and had little effect on the h2 estimate for areal BMD at other sites (h2 = 0.41-0.55, all P < 0.01). Additional adjustment for BMI, duration of diabetes, and physical activity had little effect on the h2 estimates for volumetric BMD or areal BMD except at the hip where they were lowered (h2 = 0.31-0.33, all P < 0.05). These data suggest that, like areal BMD, volumetric BMD is highly heritable and may be used in designing linkage studies to locate genes governing bone metabolism.