Background: Fetal cells can be found in the maternal circulation in most pregnancies. Fetal progenitor cells have been found to persist in the circulation of women many years after childbirth. We tested the hypothesis that microchimerism is involved in the pathogenesis of scleroderma. Scleroderma is of interest because of a strong female predilection, an increased incidence in the years after childbearing, and clinical similarities between scleroderma and chronic graft versus host disease after allogeneic bonemarrow transplantation. We also investigated whether HLA compatibility of a child was associated with the later development of scleroderma in the mother. Methods: We enrolled 40 women who had previously given birth to at least one son-16 healthy controls, 17 scleroderma patients, and seven healthy sisters of patients. We used quantitative PCR to amplify a Y-chromosome-specific sequence in whole peripheral blood from these women. Also 32 controls with 58 children, and 21 scleroderma patients with 47 children were HLA genotyped. Findings: The mean number of male cell DNA equivalents among controls was 0.38 cells per 16 mL whole blood (median 0 [range, 0-2]) and 11.1 (6.0 [range, 0-61]) among scleroderma patients (P โซุโฌ .0007). Controls' youngest sons were born a mean of 15.4 years previously, and scleroderma patients' sons 18.5 years previously. Some scleroderma patients had concentrations of male DNA higher than those found in most pregnant women. HLA-class II compatibility of a child from the mother's perspective was more common among scleroderma patients than among controls, but was not essential for the persistence of male DNA in maternal peripheral blood. Interpretation: Low concentrations of male DNA can be detected in healthy women decades after the birth of a son. Microchimerism in scleroderma patients could be secondary to the underlying disease. However, the finding that HLA class II compatibility of a child was more common for scleroderma patients than for controls, supports the possibility that microchimerism may be involved in the pathogenesis of scleroderma. COMMENTS CHIMERIC OLIGONUCLEOTIDES: AN EXCITING ANSWER THAT RAISES MORE QUESTIONS Kren BT, Bandyopadhyay, Steer CJ. In vivo site-directed mutagenesis of the factor IX gene by chimeric RNA/DNA oligonucleotides. Nature Med 1998;4:285-290. (Reprinted with permission.