Chromosome studies were performed on 11 patients with systemic sclerosis and on 35 control subjects. Nine patients with systemic sclerosis were positive for antibodies to topoisomerase I and two were negative. Of the 1100 metaphases from these 11 patients, 171 (15.5%) had chromosome breaks, compared with 61 of 3500 (1.7%) metaphases from normal control subjects. There were no statistically significant differences in the numbers of chromosome breaks between men and women. The most common fragile site in patients with systemic sclerosis was at 3p14. The karyotype of all patients was normal. Chromosome breaks did not correlate with the presence of antibodies to topoisomerase I.