The aim of our study was to establish the sensitivity of Legionella DNA detection in lower respiratory tract samples in 3 cases of Legionnaires' disease after initiation of specific antibiotic therapy. The results showed that Legionella amplicon intensity was highest in the sputum or bronchial aspirates collected at or before the start of appropriate therapy and decreased markedly within 3 days of therapy. PCR testing was negative within 4 to 6 days of therapy. These data suggest that within a few days specific antimicrobial therapy induces a significant drop of bacterial concentration in respiratory secretions reaching the detection limit of PCR assay. Respiratory samples for Legionella PCR should be obtained before or early after initiating antimicrobial therapy.