From 1988 to 1992, 27 of 855 cases of Escherichia coli bacteremia in nonneutropenic adult patients observed at our hospital were due to ciprofloxacin-resistant (CIPRO-R) strains. Eighteen episodes (67%) were community acquired, and nine (33%) were nosocomially acquired. Overall, the rates of E. coli bacteremia caused by CIPRO-R strains increased steadily from 0% in 1988 to 7.5% in 1992 (P < 0.01). There was a statistically significant correlation between the incidence of CIPRO-R E. coli bacteremia and the upward trend in fluoroquinolone (norfloxacin and ciprofloxacin) use in the community (r = 0.974; P = 0.005) as well as in the hospital (r = 0.975; P = 0.005). When we compared the 27 case patients with 54 simultaneous control patients who had ciprofloxacin-susceptible E. coli bacteremia, the case patients more frequently had chronic underlying diseases (71 versus 37%; P = 0.004), urinary tract infection (74 versus 50%; P = 0.03), prior surgery (22 versus 6%; P = 0.02), and prior fluoroquinolone use (63 versus 4%; P < 0.001). A logistic regression analysis identified prior quinolone use as the only independent risk factor for CIPRO-R E. coli bacteremia. In conclusion, our study shows a significant correlation between ciprofloxacin resistance and fluoroquinolone use and indicates that prior fluoroquinolone use seems to be the most important risk factor for CIPRO-R E. coli bacteremia.