Cell-mediated immunity is not well characterized in very low birth weight infants, and abnormalities may represent a significant vulnerability to infection. This report describes 165 serial studies in 58 infants between 700 and 1300 g birth weight during the first 8 wk of life. Two ml of blood were drawn at 2-wk intervals to measure T cell numbers and subsets and response to phytohemagglutinin (PHA). Overall, lymphocyte proliferation to PHA averaged 17,264 cpm, significantly less than the adult control (23,566 cpm). T cell numbers and subsets were CD3 62% (adult controls 75%), CD4 45% (49%), and CD8 18.6% (27%). Values at birth were lower as all parameters increased for at least the first 4 wk of life: PHA at birth was 15,464 cpm, CD3 48%, CD4 37%, and CD8 13%. Because of the lymphocytosis of premature infants, the absolute numbers of total T cells and subsets were within the normal adult range despite less than 50% of the mono-nuclear cells at birth being T cells. A study of five infants demonstrated an average of 52% B7+ cells at birth showing that the number of B cells at birth was increased approximately 10-fold over the control number in adults. Clinical correlation showed that the increases in both the % CD8 and the absolute number of CD8+ lymphocytes after birth were correlated with both the occurrence of sepsis and the number of red cell transfusions. In summary this study assessed lymphocyte subsets in a sizeable number of very low birth weight infants serially during the first 8 wk of life including lymphocyte function using isolated mononuclear cells. It demonstrated that premature infants are different from adults controls and full term newborns in: 1) having decreased lymphocyte proliferative response to PHA, 2) having lower % CD3 and CD8, and 3) having an increased number of B cells at birth.