Anterior knee pain is a frequent musculoskeletal complaint affecting all ages, both sexes, athletes, and nonathletes alike. Numerous theories have been proposed regarding its etiology including patellar malalignment, quadriceps insufficiency, subluxation, quadriceps muscle tightness, and chondral defects. However, the mechanism by which these factors produce this pain is not clear. Knowledge of the distribution of nociceptive nerve fibers around the knee would seem to provide insight in treating these painful conditions. Eleven human patellae--eight specimens from patients with degenerative patellofemoral disease and three normals--were evaluated. Immunohistochemical techniques using monoclonal antibody to substance-P were employed to identify nociceptive fibers. Substance-P is a nociceptive neurotransmitter found in afferent nerve fibers. Substance-P fibers were isolated in the retinaculum, fat pad, periosteum, and subchondral plate of patellae affected with degenerative disease. This study demonstrates that selective tracting of nociceptive pain fibers is possible around the knee both in soft tissue and, in some circumstances, bone. The subchondral plate of normal patellae did not demonstrate erosion channels, but those with chondral defects from degenerative disease did. Nociceptive fibers found in these defects may explain the origin of symptoms in some patients. The distribution of substance-P nerve fibers in the soft tissues around the knee suggests that denervation may be the mechanism by which surgical procedures for anterior knee pain produce favorable results.