When compact bone is subjected to fatigue loading, it develops matrix microdamage, which reduces the tissue's ability to resist fracture. The relative influence of different strain modes on damage and strength in compact bone has not been characterized, to our knowledge. In this study, the nonuniform strain field produced by four-point bending was used to introduce fatigue damage into tibial bending beam specimens from men 40-49 years old. The specimens were then bulk-stained with basic fuchsin to mark damage surfaces and were examined histologically and with confocal microscopy to describe damage morphologies and position relative to tension and compression-strained regions of the specimen. Histomorphometric methods were used to quantify the amounts of different types of bone microdamage. Three major types were observed. In regions subjected to tensile strains, the bone had focal regions of diffusely increased basic fuchsin staining (i.e., diffuse microdamage). Confocal microscopy of these regions showed them to be composed of extensive networks of fine, ultrastructural-level cracks. In compressive strain regions, the tissue developed linear microcracks in interstitial areas similar to those originally described by Frost. Fine, tearing-type (wispy-appearing) cracks were observed near and in the plane of the neutral axis. The paths of these fine cracks were not influenced by microstructural boundaries. Other minor damage morphologies (sector-stained osteons, delamination of regions of lamellae, and intraosteonal cracking) were observed, but their distribution was unrelated to local strain field. Thus. in fatigue of human compact bone, the principal mechanisms of matrix failure (i.e., linear microcrack, diffuse damage foci, and tearing-type damage) are strongly dependent on local strain type.