Differentiation between a cleft of the mitral valve and the cleft of the left side of an atrioventricular septal defect--a lesion commonly found in patients with Down's syndrome--is surgically important since the distribution of the conduction tissue varies between the 2 lesions. We sought to determine if cleft of the mitral valve occurs also in patients with Down's syndrome. We studied 5 patients with Down's syndrome and cleft of the mitral valve followed in our institution. Echocardiography showed in all 5 patients a cleft dividing the anterior (aortic) leaflet of mitral valve with normal papillary muscle position, mural leaflet size, and ratio of the inlet/outlet dimension of the left ventricle. Associated cardiac lesions were present in all 5 patients: perimembranous ventricular septal defect in 3, ostium secundum atrial septal defect in 2 and patent ductus arteriosus in 2 patients. During the 5.6 years (0.2-11) of the follow-up period, surgical repair of the cleft was never indicated since the mitral regurgitation through the cleft remained mild or absent in all the patients. Two patients underwent closure of a ventricular septal defect, with atrial septal defect closure in one and ductal ligation in 2. One patient died suddenly at home, without evidence of a cardiac cause. In conclusion, a cleft of the mitral valve has important developmental and morphologic differences with atrioventricular septal defect and may occur in patients with Down's syndrome. If surgical repair of the cleft or of associated cardiac lesion is indicated, it is necessary to distinguish it from atrioventricular septal defect where the conduction axis is displaced posteriorly and may be exposed during surgery.