PURPOSE: To examine the effect of intramuscular injection of botulinum toxin type A [Dysport] to reduce relative overactivity of the vastus lateralis [VL] muscle, in conjunction with re-training of vastus medialis [VM] muscle as an adjunct to rehabilitation for chronic anterior knee pain. METHOD: Eight females with chronic (>6 months) history of anterior knee pain, who had failed conservative management, were studied in this open label pilot study. Intramuscular Dysport injection [300 - 500 units] to the distal third of VL muscle was followed by a 12-week customized home exercise programme to improve recruitment of VM muscle and functional knee control. VL and VM muscle cross sectional area from a standardized spiral CT sequence, isometric quadriceps strength (dynamometry), timed stair task, self-reported pain and disability were assessed. RESULTS: Subjects reported reduced knee pain and brace dependency and increased participation in sporting and daily living activities. Isometric quadriceps muscle strength was maintained or improved despite significant atrophy, evident on CT, of the distal component of VL in the treated limb. Time taken to ascend and descend a flight of stairs improved in all subjects. Subjective and objective improvements were maintained at 24-week follow-up. CONCLUSIONS: These pilot data provide preliminary support for the role of Dysport as an adjunct to non-surgical management of individuals with chronic anterior knee pain. Larger double blind, randomized, placebo-injection controlled studies of this novel approach to improving patellofemoral mechanics are needed to establish the efficacy of this intervention.