The pathogenesis and etiology of systemic sclerosis (SSc) remain unknown, but the presence of several autoantibodies is recognized as one of its prominent features. The clinical significance of anti-DNA topoisomerase II alpha antibody (anti-topo II alpha Ab) remains unknown in Japanese patients with SSc. To determine the prevalence and clinical correlation of anti-topo II alpha Ab in Japanese patients with SSc. Serum samples were obtained from 103 Japanese patients with SSc. Control serum samples were obtained from 43 healthy Japanese volunteers. Anti-topo II alpha Abs were determined by enzyme linked-immunosorbent assay.IgG anti-topo II alpha Ab levels were significantly increased in SSc patients (n=103) compared to normal controls (n=43; P<0.005). IgG or IgM anti-topo II alpha Ab was detected in 19% (20/103) of SSc patients when absorbance values higher than the mean+2SD of control serum samples were considered positive. By contrast, IgG or IgM anti-topo II alpha Ab was observed in only 7% (3/43) of healthy individuals. The presence of pulmonary fibrosis was more frequently detected in SSc patients with IgG anti-topo II alpha Ab than those without the Ab (P<0.05). Moreover, % DLco and % VC were significantly decreased in SSc patients with anti-topo II alpha Ab relative to those without the Ab (P<0.05 and P<0.01, respectively). The elevated levels of both erythrocyte sedimentation rate and C-reactive protein were also more frequently observed in SSc patients positive for IgG anti-topo II alpha Ab (P<0.005). The results of the present study indicate that anti-topo II alpha Ab represent one of the autoantibody specificities detected on SSc patients and may be regarded a serological marker of pulmonary fibrosis in Japanese patients with SSc.