BACKGROUND: Low birth weight is generally an outcome of a fetal insult or nutritional insufficiency. Recent studies have shown that such exposure early in life may have long-term implications for later immunocompetence and susceptibility to infectious diseases. OBJECTIVE: We aimed to investigate the effect of birth weight on immune function in preschool-age children. DESIGN: A birth cohort cross-sectional study was conducted in children (n = 132) aged 60.8 +/- 0.32 mo who were born in Matlab, a rural area of Bangladesh, and whose weight and length were measured within 72 h of birth. The outcome measures were thymopoiesis, T cell turnover, acute phase response, and percentage of lymphocytes. RESULTS: Children born with low birth weight (<2500 g; LBW group, n = 66) had significantly higher concentrations of T cell receptor excision circles in peripheral blood mononuclear cells-a biomarker for thymopoiesis-and significantly higher serum bactericidal activity and C-reactive protein concentrations than did children born with normal birth weight (>or=2500 g; NBW group, n = 66) (P < 0.05 for both). The LBW group children had significantly lower concentrations of interleukin 7 in plasma (P = 0.02), shorter telomere length in peripheral blood mononuclear cells (P = 0.02), and a lower percentage of CD3 T cells (P = 0.06) than did the NBW group children. CONCLUSIONS: Greater peripheral T cell turnover (shorter telomeres and lower CD3 concentrations) due to immune activation (elevated C-reactive protein concentrations and bactericidal activity) may have resulted in a greater need for replenishment from the thymus (higher T cell receptor excision circles); these events may cause lower immune functional reserve in preschool-age children born with LBW. Thus, LBW has implications for immunocompetence and increased vulnerability to infectious diseases in later life.