During a prospective study 117 intravenous drug users were screened for infection with Corynebacterium diphtheriae. Nontoxigenic C. diphtheriae was found in 5 of 132 throat swab specimens and in 5 of 28 skin ulcer specimens taken from July 1991 to April 1992. When phenotypic and molecular typing methods were used, these 10 strains were shown to belong to a single clone. During the same period no strain was isolated from 200 controls. Clinical manifestations of infection were not clearly attributable to C. diphtheriae--no typical membranous pharyngitis was present. The presence of a single clone among homeless intravenous drug users in Zurich indicates the presence of C. diphtheriae in parts of the population with poor standards of hygiene and low socioeconomic status.