The congenital coronary lesions of piglets (Biology of the Neonate, in press) were perturbed by the primary perinatal catecholamine, norepinephrine. Newborn piglets had 45 minutes of sustained norepinephrine-induced hypertension before 4, 72, or 168 hours of baseline conditions. After euthanasia, the anterior descending coronary artery was serially sectioned for light and electron microscopy. Changes were limited to the endothelium and subendothelial intima of the most proximal segment of the anterior descending coronary artery. As similar changes are normally present in perinatal piglets, the experimental animals were compared with sham-operated controls to determine if there was a modification of the naturally-occurring congenital lesions. The increase of coronary lesions >50% circumference (15 of 33 piglets, 45%) was not statistically significant (11 of 32 control piglets, 34%); however, the experimental groups showed unique features. At 4 hours, there was marked intimal edema, disruption of the endothelium, and fragmentation and dissolution of the internal elastic lamina. There was selective invasion of the intima by monocyte-macrophages and platelets. After 72 and 168 hours there was an increase in preexisting modified smooth muscle cell plaques in which there developed prominent fibroplasia and collagenization. It is proposed that perinatal rheologic trauma to the coronary wall induced by acute hypertension may be responsible for these changes and may be an initiating factor in atherogenesis. Perinatal control of catecholamine-induced hypertension may play a role in the prevention of atherogenesis.