Several trials have shown that nonantibiotic drugs are efficacious in the treatment of travelers' diarrhea. When compared with placebo (P < .025), bismuth subsalicylate (Pepto-Bismol) taken orally at a dosage of as low as 30 ml every half hour for eight doses was shown to be effective in reducing the frequency of episodes of diarrhea. Preliminary results indicated that loperamide (two 2-mg capsules followed by one capsule after each loose bowel movement) was more effective (P < .025) than bismuth subsalicylate in relieving diarrhea. Likewise, preliminary results showed that BW942c, an unlicensed endorphin-like pentapeptide, offered more relief of diarrhea in the first 12 hr of therapy than did trimethoprim-sulfamethoxazole (P = .02) or placebo (P = .0007). Use of a nonantibiotic drug for empiric treatment of travelers' diarrhea appears to be a reasonable approach, especially for patients with mild to moderate disease and with no evidence of high fever or dysentery.