Gamma interferon (IFN-gamma) production by peripheral blood mononuclear cells (PBM) was measured in 21 patients with Crohn's disease, in 15 patients with ulcerative colitis, in 12 patients with non-IBD gastrointestinal disease (disease control), and in 28 healthy controls. T-cell subset proportions and serum levels of thymosin alpha 1 and thymosin beta 4, two hormonelike thymic peptides, were also determined. No differences were seen in T-cell subset proportions in patients with Crohn's disease or ulcerative colitis when compared to healthy controls or to the disease-control group. In vitro IFN-gamma production was markedly decreased in Crohn's disease and in untreated, but not treated, patients with ulcerative colitis. Preincubation of PBM prior to the addition of inducer mitogen resulted in enhanced IFN-gamma production in patients with Crohn's disease or ulcerative colitis which significantly exceeded that seen either in healthy controls or in the disease-control group. Serum thymosin alpha 1 levels were comparable in all study groups; however, serum thymosin beta 4 concentrations were significantly higher in all patient groups than in the healthy controls. These results confirm a defective in vitro IFN-gamma production in patients with IBD which is apparently independent of endocrine thymus regulation.