Background: Polychlorinated biphenyls (PCBs) may cause immunotoxic effects, but the detailed dose-response relationship and possible vulnerable time windows of exposure are uncertain. This study applied serum concentrations of specific antibodies against childhood vaccines as sentinels of immunotoxicity. Objectives: The main objective was to assess the possible dependence of antibody concentrations against diphtheria and tetanus toxoids in children in regard to prenatal and postnatal PCB exposures. Methods: From a cohort of 656 singleton births formed in the Faroe Islands during 1999-2001, children were invited for examination with assessment of serum antibody concentrations at ages 5 years - before and after a booster vaccination - and at 7 years. Total PCB concentrations were determined in serum from ages 5 and 7 years, and data were also available on PCB concentrations in maternal pregnancy serum, maternal milk, and, for a subgroup, the child's serum at age 18 months. Results: A total of 587 children participated in the examinations at ages 5 and/or 7 years. At age 5 years, before the booster vaccination, the anti-diphtheria antibody concentration was inversely associated with PCB concentrations in milk and 18-month serum. Results obtained two years later showed an inverse association of concentrations of antibodies against both toxoids with PCB concentrations at age 18 months; the strongest associations suggested a decrease in the antibody concentration by about 20% for each doubling in PCB exposure. At age 5 years, the odds of an anti-diphtheria antibody concentrations below a clinically protective level of 0.1 IU/L increased by about 30% for a doubling in PCB in milk and 18-month serum. Conclusions: Developmental PCB exposure is associated with immunotoxic effects on serum concentrations of specific antibodies against diphtheria and tetanus vaccinations. The immune system development during the first years of life appears to be particularly vulnerable to this exposure.