Nonsyndromic supravalvar aortic stenosis (SVAS) is an obstructive vascular disorder often inherited in an autosomal dominant manner. With pulmonary artery involvement, stenotic lesions are nearly always peripheral or downstream of the pulmonic valve. In rare cases when the supravalvar pulmonic region is affected, the stenoses usually improve over time and rarely affect prognosis. We evaluated a unique family in which 10 of 14 individuals have nonsyndromic SVAS and 7 of the 10 affected family members with SVAS have the rare finding of supravalvar pulmonic stenosis (SVPS). In at least 2 of these individuals, the severity of SVPS was so significant that it led to death in early infancy. Pathologic examination of stenotic lesions in this kindred group revealed concentrically organized smooth muscle cells separated by dense elastic fibers. In contrast, the arterial pathology reported for other individuals with nonsyndromic SVAS demonstrates increased numbers of hypertrophied smooth muscle cells separated by thin, fragmented elastin fibers. Molecular analysis identified a novel ELN mutation within the donor splice site of exon 16, which may be responsible for the unique phenotype and distinct elastin histopathology found in this kindred.