Multiple isolates of Pseudomonas cepacia, from two cystic fibrosis (CF) patients who were chronically infected and two others who suffered acute fatal lung infections, were examined by multilocus enzyme electrophoresis and four-enzyme ribotyping. The strains isolated from the fatalities belonged to a clone, electropherotype 12 (ET12) that is endemic in the Ontario patients' province of origin. ET12 strains have also been isolated from outbreaks in CF patients in the United Kingdom, where they are considered to be strains of high virulence and transmissibility and epidemiologically related to Ontario strains. Four-enzyme ribotyping (EcoRI, Xho, PstI, and ClaI) established the close genetic relationship of the Ontario ET12 isolates and those from the United Kingdom, particularly an isolate from Manchester. In addition, four enzyme ribotypes of the sequential isolates taken during life and at autopsy of the ET12 clone were highly variable in comparison with the stability of the ribotypes of clone ET16 isolated sequentially from living chronic carriers. This extreme ribotype variability may be indicative of a highly virulent strain and poor prognosis. Isolates from our chronically infected CF patients belonged to a different clone, ET16, and it is also endemic in its region, 1000 miles east of ET12, in Nova Scotia. In both endemic circumstances, person-to-person transmission was easily demonstrated by four-enzyme ribotyping. The ET12 clone was found to be transmitted among summer campers and during a nosocomial outbreak, whereas an E16 strain was found to infect a sibling of a chronically infected patient; both infections were of the same ribotype.