Background Increasing resistance to quinolones among campylobacter isolates from humans has been reported in Europe and Asia, but not in the United States. We evaluated resistance to quinolones among campylobacter isolates from Minnesota residents during the period from 1992 through 1998. Methods All 4953 campylobacter isolates from humans received by the Minnesota Department of Health were tested for resistance to nalidixic acid. Resistant isolates and selected sensitive isolates we re tested for resistance to ciprofloxacin. We conducted a case-comparison study of patients with ciprofloxacin-resistant Campylobacter jejuni isolated during 1996 and 1997. Domestic chicken was evaluated as a potential source of quinolone-resistant campylobacter. Results The proportion of quinolone-resistant C. jejuni isolates from humans increased from 1.3 percent in 1992 to 10.2 percent in 1998 (P<0.001). During 1996 and 1997, infection with quinolone-resistant C. jejuni was associated with foreign travel and with the use of a quinolone before the collection of stool specimens. However, quinolone use could account for no more than 15 percent of the cases from 1996 through 1998. The number of quinolone-resistant infections that were acquired domestically also increased during the period from 1996 through 1998. Ciprofloxacin-resistant C. jejuni was isolated from 14 percent of 91 domestic chicken products obtained from retail markets in 1997. Molecular subtyping showed an association between resistant C. jejuni strains from chicken products and domestically acquired infections in Minnesota residents. Conclusions The increase in quinolone-resistant C. jejuni infections in Minnesota is largely due to infections acquired during foreign travel. However, the number of quinolone-resistant infections acquired domestically has also increased, largely because of the acquisition of resistant strains from poultry. The use of fluoroquinolones in poultry, which began in the United States in 1995, has created a reservoir of resistant C. jejuni.