ABSTRACT: Background: We sought to determine the quantitative expression of human leukocyte antigen–DR (HLA-DR) on monocytes in patients with acute intestinal bacterial infections and inflammatory bowel disease (IBD). Methods: The quantitative expression of HLA-DR on monocytes was determined by fluorescence-activated cell sorting analysis in patients with IBD, patients with acute intestinal bacterial infections (bact.), and healthy subjects (contr.). Results: The quantitative expression of HLA-DR in patients with bact. (n = 20; 90,000 molecules per monocyte; confidence interval [CI], 79,000–102,000) was significantly higher than that in patients with ulcerative colitis (n = 40, 30,000; CI, 30,000–38,000; P < 0.0001), Crohn disease (n = 80, 31,000; CI, 32,000–39,000; P < 0.0001), or in contr. (n = 28, 39,000; CI, 36,000–46,000; P < 0.0001). In patients with ulcerative colitis and Crohn disease, HLA-DR expression was significantly decreased, as compared with contr. (P < 0.05 and P < 0.01, respectively). With a cutoff point of 50,000, HLA-DR showed a sensitivity of 95% and a specificity of 92% in discriminating between bact. and active IBD. Conclusion: The quantitative measurement of HLA-DR expression could serve as a valuable tool to discriminate between bact. and active IBD.