To study the pathogenesis of diarrhea occurring with typhoid fever, we selected 42 patients with diarrhea and blood cultures positive for Salmonella typhi or Salmonella paratyphi A, but without diarrheal copathogens, for measurement of stool output and examination of fecal composition. The mean duration of fever before hospitalization was 9.5 days, and the mean duration of diarrhea was 5.8 days. All patients passed liquid stool on their first day in the hospital, ranging in volume from 4 to 172 ml/kg with a mean of 45 ml/kg. Red blood cells were in the stools of 57% of the patients. All patients had fecal leukocytes with a mean of 4,950 leukocytes/mm3, predominantly polymorphonuclear leukocytes. In the stools, the mean protein concentration was 9.3 g/liter; the mean pH was 6.1, and the mean concentration of electrolytes was as follows: sodium, 47 mEq/liter; potassium, 48 mEq/liter; and chloride, 43 mEq/liter. The mean total CO2 was 24 mmol/liter. During treatment with chloramphenicol, this group of patients showed daily improvement with a drop in both fever and stool output. The results indicate that patients with diarrhea during typhoid fever have a wide range of rates of purging, and the diarrhea is characterized by liquid stool containing large quantities of leukocytes and protein and is resolved by treatment with chloramphenicol.