One outstanding issue regarding the relationship between elastic modulus and density for trabecular bone is whether the relationship depends on anatomic site. To address this, on-axis elastic moduli and apparent densities were measured for 142 specimens of human trabecular bone from the vertebra (n = 61), proximal tibia (n = 31), femoral greater trochanter (n = 23), and femoral neck (n = 27). Specimens were obtained from 61 cadavers (mean+/-SD age = 67+/-15 years). Experimental protocols were used that minimized end-artifact errors and controlled for specimen orientation. Tissue moduli were computed for a subset of 18 specimens using high-resolution linear finite element analyses and also using two previously developed theoretical relationships (Bone 25 (1999) 481; J. Elasticity 53 (1999) 125). Resultant power law regressions between modulus and density did depend on anatomic site, as determined via an analysis of covariance. The inter-site differences were among the leading coefficients (P < 0.02), but not the exponents (p > 0.08), which ranged 1.49-2.18. At a given density, specimens from the tibia had higher moduli than those from the vertebra (p = 0.01) and femoral neck (p = 0.002); those from the trochanter had higher moduli than the vertebra (p = 0.02). These differences could be as large as almost 50%, and errors in predicted values of modulus increased by up to 65% when site-dependence was ignored. These results indicate that there is no universal modulus-density relationship for on-axis loading. Tissue moduli computed using methods that account for inter-site architectural variations did not differ across site (P > 0.15), suggesting that the site-specificity in apparent modulus-density relationships may be attributed to differences in architecture. (C) 2003 Elsevier Science Ltd. All rights reserved.