The black yeast Exophiala dermatitidis is a frequent agent of colonization of the lungs of patients with cystic fibrosis (CF). A total of 71 clinical isolates of Exophiala from 13 patients were identified at the species level by sequencing the internal transcribed spacer (ITS) regions 1 and 2 of the rDNA genes and typed by random amplification of polymorphic DNA (RAPD), using two different primers, BG-2 and ERIC-1. In vitro susceptibility of these isolates to some systemic antifungal drugs was investigated using the CLSI method. Almost all the isolates were identified as E. dermatitidis, but long-term colonization with the closely related species E. phaeomuriformis was observed in one patient. No clustering was found according to the geographical origin of the isolates, the isolation date or the antifungal susceptibility. Variations were seen in the susceptibility of studied isolates to antifungals but most of them exhibited low susceptibility to amphotericin B and although some patients were successively colonized by two distinct genotypes, most of the isolates were distributed in patient-specific clusters. This phenomenon may be due to genomic variations of E. dermatitidis in the lung environment of CF patients. These results are typical of colonization of the airways of patients by a poorly distributed environmental fungus, which occupies particular reservoirs that need to be defined.