We studied 7 samples of lateral retinaculae excised at the time of surgical realignments. They were obtained from patients with isolated symptomatic patellofemoral malalignment resistant to conservative treatment and were evaluated with immunohistochemistry and immunoblotting. We found that neural growth factor is higher in patients with pain than in those with instability as the main symptom. Neural growth factor is related to neural proliferation in vessels and perivascular tissue and to the release of neuroceptive transmitters, such as substance P. We postulate that both mechanisms are involved in the pathogenesis of pain in isolated symptomatic patellofemoral malalignment.