Eleven (13.8%) children (4-14 months; mean of 7.8 +/- 3.6 months) presenting with protracted diarrhea (duration greater than 21 days) and weight loss had associated infection with Salmonella typhimurium. All had documented weight loss of 16-25% and progressive clinical deterioration. On admission, they had high purging rates (greater than 4 ml/kg/h), hyponatremia (5/11), mucosal injury, and malabsorption as measured by 1 h blood D-xylose, fecal alpha 1-antitrypsin, and oral fat tolerance test. Diarrhea was secretory in 8 of 11 and fecal sodium was high (54-142 mEq/L; mean of 102 +/- 27 mEq/L). The organism showed multiple drug resistance. All patients received antibiotics (amikacin and nalidixic acid/norfloxacin) for 10-14 days, which was followed by rapid improvement in clinical status and absorption studies. The two youngest patients died. Due to ethical reasons, an untreated control group was not included. Use of appropriate antibiotics may benefit children with S. typhimurium-associated severe protracted diarrhea and rapid progressive weight loss.