Systemic sclerosis (scleroderma) is a complex disease characterized by excessive deposition of collagen and abnormalities of blood vessels. In addition, activation of the immune system is a central feature of scleroderma as shown by mononuclear cell infiltration of the skin, autoantibody production and release of inflammatory cytokines. The pathogenesis of the disease is poorly understood and the molecular events underlying the main clinical features are not known. The detection of agonistic autoantibodies targeting PDGF receptor in serum of patients with scleroderma may indicate a novel link between phenotypic features of the disease and a specific signalling pathway. Agonistic PDGF receptor antibodies induce in vitro the scleroderma phenotype in normal human fibroblasts and, thus, link autoimmunity to fibrosis. These findings pave the way to novel therapeutic strategies.