The efficacy of doxycycline and ciprofloxacin against an experimental plague infection was assessed by comparing the median lethal dose (MLD) of Yersinia pestis in antibiotic-treated and untreated mice. The MLD of Y. pestis GB strain in untreated mice by the intra-peritoneal route was 23 cfu. If ciprofloxacin dosage (20 or 40 mg/kg twice daily) was initiated 48 h before infection, it afforded complete protection against an intra-peritoneal challenge of 5.24 x 10(7) cfu. Ciprofloxacin therapy initiated 24 h post-challenge was less protective, the MLD was raised to 2.0 x 10(5) and 2.2 x 10(5) cfu for 40 and 20 mg/kg respectively. Doxycycline dosage (40 mg/kg twice daily) initiated 48 h prior to infection raised the MLD to 1.6 x 10(4) cfu, but other prophylactic and therapeutic regimes were ineffective against challenges greater than 6.76 x 10(2) cfu. Ciprofloxacin may therefore be a useful antibiotic to consider for the treatment of plague.