Scleroderma skin overexpresses the platelet-derived growth factor receptor β-subunit (PDGFR-β) in dermal vessels and PDGFR-β messenger RNA in cultured fibroblasts. Moreover, increased levels of PDGF and stimulatory autoantibodies to PDGFR have been identified in the serum of scleroderma patients. Imatinib being an inhibitor of tyrosine kinase receptors such as PDGFR, its effect on scleroderma fibroblasts was evaluated in vitro as a preclinical therapeutic step. The effect of imatinib on fibroblasts grown from normal or involved/uninvolved scleroderma skin was studied by Western blot and the methyltetrazolium test. The pattern of distribution of PDGFR-β in scleroderma versus normal skin was studied by immunohistochemistry. In vitro, imatinib inhibited the proliferation of normal dermal and scleroderma fibroblasts at least partly via the inhibition of the phosphorylation of PDGFR. PDGFR-β was expressed in the epidermis and adnexae in 5 lesional scleroderma biopsies and not in controls. This study suggests that imatinib can serve as therapy to limit dermal fibroblast proliferation in scleroderma.