Many members of the Halobacteriaceae are inhibited by quinolone compounds, which inhibit type II DNA topoisomerase. Ciprofloxacin was the most potent inhibitor, followed by ofloxacin and norfloxacin. Ciprofloxacin concentrations between 25 and 60 μg/ml caused 50% inhibition of the growth of most Haloferax and Haloarcula species. Halobacterium species were less sensitive. At sublethal concentrations, formation of elongated and/or swollen cells was observed in many species. The alkaliphilic Natronobacterium pharaonis was very sensitive (50% inhibition by ciprofloxacin, ofloxacin, and norfloxacin at concentrations between 4 and 15 μg/ml). The resistance of many members of the Halobacteriaceae to high concentrations of quinolone compounds may in part be due to the high magnesium concentrations present in the growth media. Haloferax volcanii was sensitive to 40 μg/ml ciprofloxacin when grown at suboptimal magnesium concentrations (0.1 M), but was hardly affected by 100 μg/ml of the inhibitorwhen grown in the presence of 0.5-0.75 M MgCl2. It is suggested that the putative archaeal type II DNA topoisomerase has properties similar to those of the enzyme from Bacteria, although its sensitivity to quinolone antimicrobial compounds may be lower.