With the advent of newer diagnostic and therapeutic techniques in cardiology it has become more and more important that the clinician understand the functioning or three-dimensional architecture of the heart and the changes in this architecture which take place with one or another form of heart disease. A method was devised for studying at autopsy the three-dimensional structure of the heart. Approximately sixty selected normal and abnormal hearts were studied by this method, and those findings which are of clinical interest are presented. In the normal heart, the left ventricle has a relatively horizontal position in the body with its mitral and aortic orifices facing the right side of the body. The aorta makes a nearly 90 degree angle with the direction of the outflow tract of the left ventricle before it emerges from the pericardium. The right ventricle lies altogether anteriorly to the left ventricle; and the septum, which is parallel with the frontal plane of the body, is intrinsically a part of the left ventricle rather than an independent muscular partition between the two ventricles. The sequences of change in the course of development of right ventricular hypertrophy and dilatation are described. An anatomic explanation for the nearly invariable occurrence of right ventricular hypertrophy whenever left ventricular hypertrophy is marked is offered. An aspect of the pathology of mitral stenosis which has not been widely appreciated is the shortening of the posterior wall of the left ventricle. The implications of this shortening for the development of mitral insufficiency are discussed, and a striking example is presented in detail. The shortening of the posterior wall is believed to represent atrophy of this region of the left ventricle due to the immobilizing effect of the rigid mitral valve elements. It is pointed out that the shortening of the chordae tendinae of mitral stenosis is more apparent than real. The architectural changes in left ventricular hypertrophy are described. It was found that the hypertrophy tends to be circumferentially symmetric, with the septum participating equally with other regions in the hypertrophy. When the hypertrophy is marked the distal part of the outflow tract of the left ventricle is converted into a narrow conus aorticum, and evidence is offered that occasionally this narrowing may produce turbulence and obstruction to outflow from the left ventricle. The pathologic basis for the Bernheim syndrome is examined, and it is shown that the method of dissection used by Bernheim and his followers was inadequate for demonstrating obstruction of the right ventricular outflow tract. No instance of right ventricular outflow obstruction due to left ventricular hypertrophy was encountered among the hearts examined, and the existence of this syndrome is questioned. The three-dimensional changes which take place with left ventricular dilatation are described, and the role of elongation of the mitral valve e'ements in left ventricular hypertrophy and in dilatation is discussed.