BACKGROUND: Serologic data on diseases that are preventable by vaccine are useful to evaluate the success of immunization programs and to identify susceptible subgroups. OBJECTIVE: To provide national estimates of immunity to diphtheria and tetanus by measurement of serum antibody levels. DESIGN: Examination of data from the Third National Health and Nutrition Examination Survey, a representative cross-sectional sample of the U.S. population. SETTING: 89 randomly selected locations throughout the United States. PARTICIPANTS: 18 045 persons 6 years of age or older who were examined from 1988 to 1994. MEASUREMENTS: Serum samples obtained at a single time point were tested for diphtheria and tetanus antitoxin. RESULTS: Overall, 60.5% of Americans 6 years of age or older had fully protective levels of diphtheria antibody (> or =0.10 IU/mL) and 72.3% had protective levels of tetanus antibody (> 0.15 IU/mL). Ninety-one percent of Americans 6 to 11 years of age had protective levels of both diphtheria and tetanus antibody; this proportion decreased to approximately 30% among persons 70 years of age (29.5% for diphtheria and 31.0% for tetanus). Adult Mexican-Americans were slightly less likely to have protective levels of antibody to both toxins. Only 47% of persons 20 years of age or older had levels that were protective against both diseases, and only 63% of adults who were protected against tetanus were also protected against diphtheria. CONCLUSIONS: A substantial proportion of adults in the United States do not have antibody levels that are protective against diphtheria and tetanus. In addition, although the recommended vaccine is a combination of tetanus and diphtheria, only 63% of adults with protective antibody to tetanus also had protective antibody to diphtheria.