HLA-A, B, C, and DR antigens were studied in 27 Viennese patients with Crohn's disease and 30 patients with ulcerative colitis. The frequency of HLA-B12 was found to be significantly (p less than 0.001, pc less than 0.05) increased in patients with Crohn's disease (52%) as compared with both healthy controls (21%) and patients with ulcerative colitis (10%). The frequency of HLA-Cw5 was slightly increased in Crohn's disease; however, the corrected p value was not significant. With regard to HLA-DR antigens, differences between the study groups and the controls or between ulcerative colitis and Crohn's disease did not reach statistical significance. However, the concomitant occurrence of HLA-B12 and/or Cw5 and/or DR7 was observed in 11 Crohn's disease and no ulcerative colitis patient (pc less than 0.006); there is a known linkage disequilibrium between these antigens. Although they differ from previous reports, these data in conjunction with the recently disclosed increased HLA recombination frequency in patients with Crohn's disease indicate that genes coding for HLA antigens may play a role in the pathogenesis of Crohn's disease.