Cutis marmorata telangiectatica congenita (CMTC) is a rare cutaneous vascular disease presenting at birth with levido reticularis, phlebectasia, and telangiectasia, often accompanied by skin ulcerations. Extra-dermal vascular anomalies can be also detected in 30–70% of described cases. The pathomechanism responsible for development of these phenotypic changes is not well understood. Here, we report on a 16-month-old boy with CMTC, generalized vascular abnormalities and severe, nitric oxide sensitive, pulmonary hypertension associating with markedly elevated level of blood copper. Results of laboratory investigations indicated that primary cultures (passage one) of dermal fibroblasts derived from this patient were capable of normal synthesis of tropoelastin, but their net deposition of mature elastic fibers was significantly diminished as compared with cultures of normal fibroblasts. Because the low net deposition of elastin was reversed when 1 mg/ml of α1-antitrypsin was added to the media, we conclude that heightened elastolysis by endogenous serine proteinase's is responsible for the low net elastogenesis by CMTC fibroblasts. Since simultaneous addition of 30 µM CuSO4 and 1 mg/ml α1-antitrypsin abolished the beneficial effect of this serine proteinase's inhibitor, we concluded that this may be due to copper-dependent inactivation of α1-antitrypsin. Our data suggest that a high level of free copper may constitute a major triggering factor contributing to the development of the CMTC phenotype. © 2008 Wiley-Liss, Inc.