The incidence and time of occurrence of pulmonary vascular disease were studied in 67 children with the complete form of atrioventricular (A-V) canal defect. Advanced pulmonary vascular disease begins to develop during the first year of life, with intimal fibrosis (grade 3 cahnges) noted between age 6 months to 1 year. Vascular dilatation with plexiform lesions (grade 4 changes) can be found by age 1 year. These changes can be found in some patients in spite of hemodynamic findings usually considered to indicate lesser degrees of vascular disease. After age 2 years advanced pulmonary vascular disease is commonly found and may persist after surgical correction of the defects. A similar rapid progression of pulmonary vascular disease was noted in 40 children who had a large ventricular septal defect without A-V canal in whom systemic pressure was transmitted directly to the pulmonary vascular bed. Thirty-six of the 67 children had trisomy-21. No difference was noted in the speed of progression of pulmonary vascular disease between these children and those without trisomy 21. Palliative or corrective surgery should be performed in these patients by age 1 year to prevent development of advanced pulmonary vascular disease.