Select soft tissues in clubfeet are contracted, resulting in stiffness. These contracted tissues share ultrastructural characteristics with palmar fibromatosis (Dupuytren contracture), in which the growth factors transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) are expressed and play a role in regulating cell behavior. More contracted tissue (medial side of the foot) and less contracted tissue (lateral side of the foot) from 20 clubfeet were studied using reverse transcription-polymerase chain reaction and western analysis for expression of TGF-beta and PDGF (along with collagen type I and type III). Cell cultures were established from the more contracted tissues to determine the effect of blockade of these factors with neutralizing antibodies on proliferation, chemotaxis, and collagen expression. Both growth factors were expressed at higher levels by the contracted tissues, and blockade led to decreased collagen expression, proliferation, and chemotaxis. Growth factor blockade has the potential to change the behavior of these cells in a way that would lessen the severity of the contractures, perhaps improving the outcome of clubfoot treatment.