Two clinical trials in adults in Mexico are reported. In the first trial, long-term residents of Mexico with acute fecal leukocyte-positive diarrhea were randomized to receive trimethoprim/sulfamethoxazole (TMP/SMX), clioquinol or a placebo. Neither antimicrobial shortened the illness for all cases or for those with shigellosis or enterotoxigenic Escherichia coli diarrhea. In a second study, US and Mexican students received enoxacin, TMP/SMX or a placebo on a blind random basis. While the placebo-treated subjects with bacterial diarrhea tended to be more ill after treatment than other groups, no statistical differences were seen in treatment groups. These studies cast doubts on the value of antimicrobial drugs for ‘invasive’ and other forms of bacterial diarrhea in adults living in endemic areas and indicate the importance of a placebo control group when conducting clinical trials in these populati