Soft tissue injuries due to repetitive motion are common sports injuries and are often treated with antiinflammatory therapies. We investigated the in vitro effects of repetitive motion and nonsteroidal antiinflammatory medication on human tendon fibroblasts. In addition, we studied the effects related to the presence of inflammatory cells. Repetitive motion was associated with an increased release of prostaglandin E2 and increased deoxyribonucleic acid (DNA) and protein synthesis. The presence of nonsteroidal antiinflammatory medication decreased prostaglandin E2 release and DNA synthesis but increased protein synthesis. Contact with macrophages caused a marked additional increase in prostaglandin E2 and a concomitant increase in DNA synthesis. Release of interleukin-6 by the macrophages also suggested that this cytokine plays a role in the response to repetitive motion. Our results can aid in the search for a more scientific approach to the treatment of soft tissue injuries associated with repetitive motion. They suggest that nonsteroidal antiinflammatory medication may have potentially negative effects during the proliferative phase of a healing since it was associated with decreased DNA synthesis. However, it may be beneficial in the maturation and remodeling phase since it stimulated protein synthesis.