A semiquantitative indirect immunofluorescence assay to detect coproantibody secretory IgA (SIgA) was established to investigate the human intestinal immune response to Yersinia species. This assay was based on microagglutination of SIgA in fecal specimens with the patient's homologous organism. Two populations of patients were defined, those who produced an agglutinating (2+) SIgA response and those who did not. A comparison between SIgA production and standard in vitro virulence-related characteristics of infecting organisms, including autoagglutination, calcium dependence, plasmid carriage, and absorption of Congo red, mouse virulence, and clinical presentation, was performed. A positive (2+) SIgA result was associated with acute enteric illness (positive predictive value, 78.6%) and mouse virulence (positive predictive value, 85.7%). When patients with active inflammatory bowel disease were excluded, the positive predictive value of SIgA for mouse virulence and acute enteric disease became 100%. In addition to strains of Yersinia enterocolitica 4,O:3, strains generally characterized as nonpathogenic, including Yersinia frederiksenii, were found to be associated with acute disease, mouse virulence, and stimulation of SIgA. The indirect immunofluorescence assay for detection of SIgA response appears to be a useful indicator of pathogenic strains of yersiniae recovered from enteric specimens.