Staphylococcus aureus is the principal etiological agent of osteomyelitis (bone infection), which is characterized by a progressive inflammatory response resulting in extensive damage to bone tissue. Recent studies have demonstrated the ability of S. aureus to invade and persist inside osteoblasts (bone matrix-forming cells) and other eukaryotic cells. The presence of intracellular S. aureus in bone tissue may be relevant to the pathology of osteomyelitis, a disease often refractory to antibiotic treatment and subject to recurrence months and even years after apparently successful therapy. The present study examined the production of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) following S. aureus infection, and whether expression of the molecule was induced by those osteoblasts containing intracellular S. aureus. Results from this study suggest that osteoblasts containing intracellular S. aureus induce TRAIL expression in uninfected osteoblasts present in infected cultures.