Since 1985, nosocomial infections have been frequently treated with a new fluoroquinolone, pefloxacin, at the Cardiological and Neurological Hospital in Lyon. From 1986 to 1988, the incidence of resistance of clinical Staphylococcus epidermidis strains to pefloxacin increased from 31 to 57%. Dispersion of these resistant strains in the hospital environment was recognized when they were detected on 22% of staff members' fingers (139 samples were investigated) and in 28% of the environmental samples (180 were investigated). There was an association between carriage rate and work place. Most of the pefloxacin-resistant S. epidermidis were resistant to oxacillin, gentamicin, erythromycin, cotrimoxazole and fosfomycin. Intensive use of pefloxacin selected multiresistant S. epidermidis which became ubiquitous in the hospital environment.