Pressure overload of cat right ventricle causes progressive abnormalities of in vitro contractile function at a time when in vivo contractile function is normal. In marked contrast, the same degree and duration of volume overload of cat right ventricle results in neither in vitro nor in vivo contractile dysfunction. The purpose of the present quantitative structural study was to determine whether there were any histological alterations in pressure-overloaded myocardium that might be causally related to the contractile dysfunction found only in this model. Four experimental groups of eight cats each were studied: a group with pulmonary arterial banding to create a pressure overload, sham-operated controls for this group, a group with atrial septal defects to create a volume overload, and sham-operated controls for this group. Seven to ten weeks after each operative procedure, right ventricular pressure was elevated only in the pressure-overloaded group, pulmonary-to-systemic blood flow ratio was increased only in the volume-overloaded group, and right ventricle-to-body weight ratio was significantly and comparably increased in both the pressure- and the volume-overloaded groups. There was a single striking histological distinction between myocardium hypertrophying in response to pressure as opposed to volume overload: the volume density of cardiocytes in papillary muscles from pressure-overloaded right ventricles was decreased significantly with a proportional increase in connective tissue. Given the critical importance of these two myocardial components to both systolic and diastolic cardiac function, these data provide a potential structural basis for at least some of the functional abnormalities observed in pressure but not in volume overload hypertrophy of the cat right ventricle.