The activity of an interferon induced enzyme, (2',5') oligo adenylate synthetase, was determined in peripheral blood mononuclear cells and granulocytes of patients with inflammatory bowel disease and compared with its activity in cells isolated from normal subjects. In spite of the fact that circulating interferon is detected in patients with inflammatory bowel disease, we failed to see any increase in (2',5') oligo adenylate synthetase activity in these patients. The mean +/- SE enzyme activity given in nmol ATP incorporated into (2',5') isoadenylate oligomers by extracts of 10(5) peripheral blood mononuclear cells/21 hours was in normal subjects 1.84 +/- 0.30 (n = 27), in patients with active Crohn's disease 1.38 +/- 0.15 (n = 20) and in patients with active ulcerative colitis 1.14 +/- 0.23 (n = 21). (2',5') oligo adenylate synthetase activity in granulocytes was also similar in normal subjects and in patients with active ulcerative colitis or Crohn's disease. The enzyme activity in patients with active disease was similar both prior to and during steroid therapy. The low (2',5') oligo adenylate synthetase activity in peripheral blood mononuclear cells and granulocytes of patients with active inflammatory bowel disease may reflect decreased cellular response to interferon or a difference in the type of interferon elevated in viral diseases and in inflammatory bowel disease.