Fracture toughness tests were conducted in the transverse and longitudinal directions to the osteonal orientation of human femoral cortical bone tissue to investigate the resulting damage patterns and their interaction with the microstructure. The time history of damage accumulation was monitored with acoustic emission (AE) during testing and was spatially observed histologically following testing. The fracture toughness of the transverse specimens was almost two times greater than the fracture toughness of the longitudinal specimens (3.47 MNm(-3/2) vs. 1.71 MNm(-3/2), respectively). The energy content of the AE waveforms of transverse specimens were greater than those of the longitudinal specimens implying higher fracture resistance in the transverse crack growth direction. The results showed that the propagation of the main crack involved weakening of the tissue by ultrastructural (diffuse) damage at the fracture plane and formation of linear microcracks away from the fracture plane for the transverse specimens. For the longitudinal specimens, the growth of the main crack occurred in the form of separations at lamellar interfaces. The lamellar separations generally arrested at the cement lines. Linear microcracks occurred primarily in the interstitial tissue for both crack growth directions.