The profile of antinuclear antibodies (ANA) in 49 Thais with scleroderma (systemic sclerosis) was compared with that in 68 white Australians with scleroderma. Forty-eight (98%) of the Thais and all (100%) of the white Australians were positive for ANA, with the majority (100% and 97%, respectively) showing a diffuse speckled pattern of nuclear fluorescence. The distribution of the patterns was different in the 2 races; 35 (71%) of the Thais and 17 (25%) of the Australians showed staining of the nucleolus, and 1 (2%) of the Thais and 35 (51%) of the Australians showed staining of the centromeres. The frequency of precipitating antibodies to extractable nuclear antigens was also strikingly different: 86% in Thais and 26% in Australians (P less than 0.001). Precipitating antibodies to Scl-70 (topoisomerase I), the predominant extractable nuclear antigen in patients with scleroderma, were detected in 37 (76%) of the Thais and 18 (26%) of the Australians, and these were shown by Western blotting to react with the Scl-70 (topoisomerase I)-associated polypeptides. Differences in the frequencies of the ANA specificities in the 2 races were consistent with differences in the clinical manifestations of scleroderma; all of the Thai patients, in contrast to 15% of the Australian patients, had diffuse scleroderma with widespread skin involvement. This suggest that environmental or genetic factors may influence the expression of scleroderma.