We studied the immune response to acute diarrhea by examining antibody-secreting cells among peripheral blood lymphocytes, which are believed to be derived from the intestinal mucosa and to be on their way back there. In 23 of 24 patients, a dramatic increase in the total number of cells actively secreting immunoglobulins was detected one week after onset of diarrhea, and most of the cells were secreting IgA. Cells secreting antibody specific to the pathogen (Campylobacter jejuni or Salmonella spp.) also appeared at this time but accounted for only a part of the total response. The data suggest that diarrhea induces a vigorous, apparently polyclonal response, including antibodies to normal intestinal flora. The response to the infective agent was outstanding and suggests that this method can be used to identify the causative agent of an infection.