Pefloxacin was compared to erythromycin in the treatment of guinea pigs severely infected with Legionella pneumophila. In this experimental model, two single intraperitoneal injections of either pefloxacin (10 mg/kg at 48 h and 5 mg/kg at 55 h) or erythromycin (40 mg/kg at 48 and 55 h) were administered 48 h post-infection (2 X 10(7) virulent L. pneumophila intraperitoneally). Counts of bacteria in blood monocytes and lungs of animals killed at different times after the completion of treatment, demonstrated a quick and highly significant reduction of the pretreatment bacterial load in pefloxacin-treated guinea pigs. Conversely, in erythromycin-treated animals the number of bacteria was only slightly reduced 17 h after the completion of the treatment and then multiplication up to pre-treatment levels occurred. The overall mortality was significantly lower in pefloxacin-treated animals with this therapeutic protocol. The remarkable results of pefloxacin in this model, were obtained with serum and lung levels of this drug lower than those achieved in man with the currently accepted regimens. Thus, pefloxacin appears to be a new promising antimicrobial agent for Legionnaire's disease.