Fifty-two patients with isolated congenital ventricular septal defects (VSDs), studied for the first time at age 10 or older, were restudied an average of 16 years later (range 4 to 21). The study protocol included a symptom-limited bicycle ergometer test, M mode echocardiographic examination, and hemodynamic studies at rest and during mild supine exercise. Of the 52, 17 had been operated on an average of 19 years earlier (range 11 to 21) (group 1) and 35 with smaller defects were not operated on (group 2). Although more pronounced findings were made in group 1, a similar pattern was observed in group 2: In most subjects in both groups a subnormal working capacity was observed. A subnormal left ventricular fractional shortening and circumferential shortening velocity was noted in a high proportion at echocardiography. A number of hemodynamic aberrations were observed in a high proportion of patients during exercise but not at rest. Thus a subnormal increase in left and right ventricular cardiac output was found in addition to pathologic increase in right and left ventricular end-diastolic, pulmonary arterial, and pulmonary capillary wedge pressures. In group 1, elevated pulmonary arterial pressures before operation and/or small residual VSDs were associated with a poor hemodynamic outcome. In neither group could significant correlations be observed between hemodynamic aberrations, shunt size, and/or age. Among patients who underwent surgery, the earlier surgical trauma might have contributed to the functional aberrations, but in group 2 the only likely explanation for the findings seems to be the VSD itself. Possibly a long-standing VSD--found unnecessary to repair according to commonly accepted criteria--may lead to disturbed systolic function and increase in compliance of both ventricles via a chronic pressure and volume overload.