Immunohistochemical, flow cytometric and ELISA studies were performed to examine the expression of endoglin (CD105, a TGF beta receptor) on dermal endothelial cells, peripheral blood monocytes and free and bound serum levels in patients with systemic sclerosis as compared with appropriate controls. Endoglin was found to be significantly upregulated on dermal blood vessels in patients with scleroderma (and in patients with inflammatory skin disorders) as compared to healthy skin (p < 0.05). In contrast, there was no significant difference in endoglin expression on circulating blood monocytes between scleroderma patients and patients with a rheumatic disoder or healthy control subjects; however, endoglin expression was upregulated on monocytes in inflammatory joint fluid from patients with rheumatoid arthritis. Endoglin expression on monocytes was also influenced by isolation techniques and during whole blood culture. No differences were found in circulating free or bound endoglin levels between scleroderma patients and healthy controls. In conclusion, endoglin expression on dermal endothelial cells was significantly enhanced in scleroderma but levels on circulating monocytes and in the serum were within normal limits. The functional significance of this upregulation is uncertain but may reflect endothelial activation in scleroderma.