In a randomized clinical trial, norfloxacin was compared with nalidixic acid in the treatment of acute invasive diarrhea, with particular reference to shigellosis in adults. Of 104 patients studied, 40 were positive for Shigella in stool cultures, of which 22 received norfloxacin and 18 received nalidixic acid. The patients in these two groups were comparable on admission. In the treatment of culture-positive shigellosis cases, the responses to therapy with both drugs were similar, except that the duration of fever, anorexia, and abdominal pain were less in those who received norfloxacin. Norfloxacin appeared to be superior to nalidixic acid in the treatment of shigellosis cases caused by Shigella strains resistant to nalidixic acid.