Ciprofloxacin, unlike nalidixic acid, can kill Escherichia coli cells in the absence of synthesis of protein or RNA. Hence, chloramphenicol or rifampicin do not abolish the bactericidal activity of ciprofloxacin against wild-type E. coli. Protein and RNA synthesis were not required for the bactericidal activity of ciprofloxacin against nalB, nalC and nalD mutants of E. coli. However, the addition of chloramphenicol or rifampicin abolished the bactericidal activity of ciprofloxacin against a nalA mutant in nutrient broth. It is concluded that the ability of ciprofloxacin to kill E. coli in the absence of protein or RNA synthesis involves the A subunit of DNA gyrase.