Lethal perinatal osteogenesis imperfecta (OI Type II) is a biochemically diverse collagen disorder characterized by short, crumpled long bones, beaded ribs, blue sclerae and thin, fragile skin. Cardiovascular abnormalities are rarely described. Using morphometry and light and electron (SEM and TEM) microscopy, we analyzed the hearts and great vessels from 2 fetuses with OI Type IIA and compared the findings with age-matched controls. The heart weights and atrioventricular valve (AVV) circumferences were reduced in OI. The chordae tendineae were short and fragile; both the AVVs and the chordae tendineae were hypercellular. TEM showed relatively little organized collagen in the chordae tendineae of OI fetuses. Furthermore, quantitative evaluation of collagen fibril size revealed a decrease in the cross-sectional diameter. There was also a marked decrease in the adventitial and intramural collagen of the intramyocardial arteries and great vessels in OI. Our study reports, for the first time, specific lesions in the cardiovascular systems of patients with OI Type II and reviews the cardiovascular pathology in other forms of OI.