Groups of healthy, small-for-gestational age (SGA) and preterm appropriate-for-gestational age (AGA) infants were studied at birth, 1 month, 3 months, and 12 months of age. Serum thymic hormone (TH) activity was assayed, the number of T lymphocytes in the peripheral blood was counted, and in vitro lymphocyte stimulation responses to phytohemagglutinin (PHA) were evaluated. TH activity was decreased in 1-month-old SGA infants. T cells were reduced in all low birth weight infants; the number reverted to normal by 3 months of age in preterm AGA infants, whereas it remained low for at least 12 months in the SGA group. Lymphocyte stimulation response was decreased in low birth weight infants; the extent of depression paralleled reduction in T lymphocyte number. These observations indicate that cell-mediated immunity is impaired in low birth weight newborns and reduced TH activity may be one of the pathogenetic factors involved. Persistent depression of immunocompetence may underlie the increased susceptibility of SGA infants to infection-related morbidity and mortality.