It is reported that fibroblasts derived from clinically affected skin areas of patients with systemic sclerosis (SSc) have the ability to overproduce several cytokines and growth factors (i.e., IL-6, PDGF), an ability that might be involved in the pathogenesis of SSc. We have previously shown that the expression of IL-1α was constitutively observed in SSc fibroblasts, whereas this was not detected in normal fibroblasts. Although it was suggested that the aberrant IL-1α production could be associated with the fibrogenic phenotype of SSc fibroblasts, little is known about the roles of IL-1α in SSc fibroblasts. IL-1α induced IL-6 and PDGF-A, which are potent stimulators of collagen production and proliferation in normal fibroblasts. This article examines the proposal that IL-6 and PDGF-A are elevated through the action of endogenous IL-1α in SSc fibroblasts. An antisense oligodeoxynucleotide complementary to IL-1α mRNA was used to suppress endogenous IL-1α. Inhibition of endogenous IL-1α led to decreased levels of IL-6 and PDGF-A expression in SSc fibroblasts. Moreover, the blocking of the IL-6 response using anti–IL-6 antibody resulted in a significant reduction of procollagen type I in cultured SSc fibroblasts. These results suggest that endogenous IL-1α expressed by SSc fibroblasts may play a key role in the abnormal function of SSc fibroblasts through the expression of IL-6 and PDGF-A.