Intestinal perforation, a life-threatening complication of toxic megacolon (TM) following non-typhoid Salmonella infection, is relatively uncommon in infants less than 1 year of age. The situation, also found in typhoid fever, appears to be cytokine-mediated. This finding may justify immunotherapy for older children with TM associated with non-typhoid Salmonella infection in order to prevent this complication.