• Thirty-two infants younger than 6 months with catheterization-proved congenital heart disease were prospectively examined for T-lymphocyte immunodeficiency (compared with adult and normal newborn controls). Cardiac lesions were separated into two groups: (1) "high-risk" lesions previously associated with T-cell abnormalities in DiGeorge's syndrome, and (2) the remaining "low-risk" lesions. Cardiac patients as a whole did not have significant abnormalities in T-cell rosette (TCR) percentages (mean ± SE, 50.0%±22%) or response to phytohemagglutinin (PHA) (72,243±38,388 counts per minute). However, a greater percentage of patients with high-risk cardiac lesions had abnormal TCR and PHA results than either the control or low-risk group, due to the inclusion of three infants with DiGeorge's syndrome. These findings suggest that newborn infants without evidence of DiGeorge's syndrome have normal T-lymphocyte function. Infants with high-risk cardiac lesions deserve a careful immunologic evaluation to avoid significant morbidity and mortality.