Trimethoprim/sulfamethoxazole is currently considered the treatment of choice for shigellosis and severe travelers' diarrhea. The problem with this combination regimen is inactivity against Campylobacter jejuni strains and other bacterial enteropathogens showing in vitro resistance to the drug. Resistance to trimethoprim/sulfamethoxazole among enteric pathogens has occurred frequently in certain areas of the world. A study of the in vitro susceptibility of enteric bacterial pathogens isolated from multiple countries was recently performed. The minimal inhibitory concentration of ciprofloxacin required to inhibit 90 percent of the 210 bacterial enteropathogens ranged from 0.25 micrograms/ml for C. jejuni to 0.016 micrograms/ml for enterotoxigenic Escherichia coli, Salmonella, and Shigella. In a clinical trial carried out in a United States student population that acquired diarrhea while in Mexico, it was shown that ciprofloxacin was as effective as trimethoprim/sulfamethoxazole and both were significantly (p less than 0.001) more effective than placebo. The average duration of diarrhea was 29 or 20 hours after initiation of treatment with ciprofloxacin or trimethoprim/sulfamethoxazole, respectively, compared with 81 hours in the placebo group. The antimicrobial agents were more efficacious than placebo in treating diarrhea caused by enterotoxigenic E. coli, invasive enteropathogens, and unknown pathogens. Ciprofloxacin and the quinolone derivatives are uniquely suited to the therapy of acute bacterial diarrhea in areas where C. jejuni is commonly found and where trimethoprim/sulfamethoxazole-resistant strains regularly occur.