Fetal progenitor cells traffic to the mother during pregnancy and can persist in the maternal circulation for many years. Feto-maternal microchimerism has been reported in women with scleroderma, but its contribution to the disease pathogenesis remains unclear. Furthermore, the involvement of microchimerism in other connective tissue diseases is controversial. We studied 243 females, 122 of whom had previously carried a male fetus (50 healthy controls, 23 patients with scleroderma, and 49 with other connective tissue diseases). The presence of the male-specific SRY sequence was analyzed using a kinetic quantitative ELISA PCR assay that allows detection of one to three male cells in one million female cells. The percentage of SRY-positive samples was not different among women having borne son(s): 16% (95% confidence interval 0.07-0.29) in healthy controls, 21.7% (0.07-0.44) in patients with scleroderma and 25.5% (0.14-0.40) in patients with connective tissue diseases (p=0.25). The mean number of fetal cells was similar in the three groups. Among the 121 females who never carried a male fetus, no healthy woman was SRY positive. However, 33% of patients with scleroderma and 22.9% of women with connective tissue diseases were chimeric, a phenomenon which might be related to early miscarriage(s). Therefore, feto-maternal microchimerism is a common event in both healthy controls and patients with connective tissue diseases, and is unlikely to represent per se a risk factor for these diseases.