In this double-blind study with 232 patients, 300 mg of ofloxacin given orally twice daily for 5 or 3 days was compared with placebo for the treatment of acute diarrhea in U.S. students visiting Guadalajara, Mexico. The 3-day regimen of ofloxacin was found to be as effective as the 5-day regimen in producing a clinical and microbiologic cure. Clinical cures for patients who received ofloxacin for 5 days occurred in 59 of 66 (89%) subjects, whereas clinical cure occurred in 77 of 81 (95%) of those who received ofloxacin for 3 days and in 56 of 79 (71%) of those who took placebo (P = 0.0001). When the duration of diarrhea after therapy was begun was compared in subgroups, a significant (P less than 0.05) shortening of posttreatment illness occurred in comparison with that in the placebo group for the following groups: for 5 days of ofloxacin, cases of shigellosis (32 versus 98 h); for 3 days of ofloxacin, all cases (28 versus 56 h), cases of enterotoxigenic Escherichia coli diarrhea (26 versus 66 h), cases of shigellosis (24 versus 98 h), all cases of illnesses associated with a bacterial enteropathogen (28 versus 69 h), and cases of illnesses in which numerous leukocytes were found in stool by microscopy (22 versus 49 h). Microbiologic eradication rates were 75 of 78 (96%) for patients who received ofloxacin and 37 of 46 (80%) for patients who received placebo (P = 0.009). There was no significant difference in the number of adverse events reported by patients in either of the treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)