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The Public Health Laboratory Service receives antibiotic susceptibility data for bacteria from bloodstream infections from most hospitals in England and Wales. These data were used to ascertain resistance trends to ciprofloxacin from 1990 through 1999 for the most prevalent gram-negative agents: Escherichia coli, Klebsiella spp., Enterobacter spp., and Proteus mirabilis. Significant increases in resistance were observed for all four species groups. For E. coli, ciprofloxacin resistance rose from 0.8% in 1990 to 3.7% in 1999 and became widely scattered among reporting hospitals. The prevalence of resistance in Klebsiella spp. rose from 3.5% in 1990, to 9.5% in 1996 and 7.1% in 1999, while that in Enterobacter spp. rose from 2.1% in 1990 to 10.5% in 1996 and 10.9% in 1999. For both Klebsiella and Enterobacter spp., most resistance was localized in a few centers. Resistance was infrequent and scattered in P. mirabilis, but reached a prevalence of 3.3% in 1999.