Two hundred Pseudomonas aeruginosa serial isolates from 61 cystic fibrosis patients were examined using restriction fragment length polymorphism in connection with pulsed field gel electrophoresis. A comparison was made of results obtained by genome fingerprinting and by conventional typing methods. It was possible to subdivide the majority of the genome types with the conventional typing methods, indicating the likelihood of bacterial phenotypes occurring in the lung of the cystic fibrosis patient. Two clusters of strains were observed among the 200 P. aeruginosa isolates from the 61 patients. Strains belonging to one cluster were present in 26 (42.6%) of the 61 patients. Strains belonging to the other cluster were present in 11 (18.0%) of the 61 patients. The occurrence of these clusters indicates that cross-infection has taken place among CF patients attending the Danish Cystic Fibrosis Centre. Conventional typing methods are based on the presence of specific bacterial surface structures. Therefore, conventional typing methods may sometimes lead to wrong classification of isolates from cystic fibrosis patients, especially if applied alone. A combination of two to six methods decreased the reproducibility of the typing results. The best combination was genome fingerprinting and phage typing, which yielded a reproducibility of 82.5%. Each time a method is added, the reproducibility decreases by an average of 14.4%.