Structural changes in the pulmonary circulation were studied in the lungs of 5 infants dying with ventricular septal defect. Applying precise quantitative morphological techniques to the pulmonary vessels, it was possible to correlate pathological change with clinical and haemodynamic findings, and to identify two patterns of response. Three of the infants (group I) ppresnted in cardiac failure with a large pulmonary blood flow, dilated and tortuous pulmonary arteries, and fewer intra-acinar vessels than normal. Medial hypertrophy was moderate and affected chiefly the larger arteries, i.e. those with a diameter greater than 200 mum. The other 2 infants (group 2) had a high pulmonary vascular resistance with an intermittent right-to-left shunt. The pulmonary arteries were of normal size and the reduction in the number of the arteries was less striking. Medial hypertrophy was greater than in the first group and affected all sizes of artery including those less than 200 mum in diameter. In both groups, muscle extended further along the axial pathway. Muscular hypertrophy was found also in the vein wall in most cases and, as with the arteries, was more severe in those with a higher pulmonary vascular resistance. The findings illustrate the variation in pulmonary vascular response in infants with a ventricular septal defect. It is suggested that in patients with a ventricular septal defect, arterial muscularity usually regresses after birth and a left-to-right shunt develops; secondary hypertrophy of the media then develops in reaponse to the shunt. Our findings also suggest, however, that in some infants arterial muscle fails to regress postnatally so that pulmonary blood flow is never high and a right-to-left shunt develops soon after birth.