Renal cortical necrosis, renal medullary necrosis, and combined renal cortical-medullary necrosis result from renal ischemia without vascular occlusion. Renal hypoperfusion and ischemic injury in infants have been ascribed to massive blood loss, hemolytic disease, septicemia, and severe hypoxemia. In a postmortem study we identified 82 cases among 1,638 autopsies during the 20 years between 1970 and 1989 in infants 3 months old or less at the time of death. The frequency of renal necrosis in autopsy cases increased significantly during the last 6 years of the study. The distribution of the renal lesion was cortical in 28, medullary in 23, and combined in 31. Forty infants carried diagnoses of congenital heart disease, 17 of asphyxial shock, 9 of sepsis, 3 of infectious myocarditis, 9 of major malformations, 4 of anemic shock, 1 of vascular malformation, and 1 of gastroenteritis and dehydration. A significantly higher proportion of babies with congenital heart disease had cortical involvement. Comparison of clinical characteristics revealed a significantly higher frequency of prematurity, respiratory distress syndrome, bleeding diathesis, and possibly sepsis in the children with congenital heart disease, suggesting that these factors are important in the pathogenesis of the renal lesion. Fourteen infants underwent cardiac catheterization; there was no demonstrable association between the renal lesions and the use of radiographic contrast medium. We conclude that severe congenital heart disease itself is a risk factor for life-threatening renal cortical and medullary necrosis.