A two-part study was carried out in Alaskan Native children to evaluate the potential risk of invasive bacterial disease and the occurrence of minor illnesses after immunization with diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTP). First, a case-control comparison was performed with 186 children who had invasive Haemophilus influenzae type b or Streptococcus pneumoniae disease (cases) and 186 healthy controls matched for sex, region of residence, birth date, and number of DTP immunizations. The proportion of cases and controls immunized in the 30-day period before onset of disease for cases or reference date for controls was identical, suggesting no association with DTP immunization. In a second analysis, the occurrence of any illness, particularly infectious diseases, in 104 study subjects was compared for the period 30 days before and after 377 DTP immunizations. The rate of illness before immunization was 53%, and after immunization, 43%, again suggesting no causative effects from DTP immunization. Despite the high rates of invasive bacterial disease and nearly compete DTP immunization status in this population, no consistent relationship could be demonstrated between DTP immunization and susceptibility to infectious diseases.