In 2004, the reported incidence of pertussis in the United States nearly tripled compared with 2001, and the number of reported cases exceeded any year since 1959.8 This increase might have resulted, in part, from increased use of more sensitive PCR testing.8 CDC recommendations call for culture confirmation of infection in one or more cases in an outbreak. However, in the outbreak described in this report, no culture confirmation was performed. The medical staff at children's hospital A requested PCR testing, as did the local health department. Current molecular detection methods for detection of B. pertussis have high sensitivity compared with culture, but occasionally can be prone to false positives, depending on the target sequences, interpretation of results, and subjects tested.9 In a recent report describing outbreaks of respiratory illness mistakenly attributed to pertussis, PCR was used inappropriately as a mass screening tool on a large number of persons who did not meet the CSTE case definition for pertussis.9 For the infants described in this report, a high index of suspicion for pertussis was based on clinical symptoms, and PCR testing was used to confirm diagnoses of pertussis. HCW A also met the CTSE case definition for pertussis.