We have examined the concentration of immunoglobulin G (IgG) subclass antibodies in the sera of 27 patients with ulcerative colitis and 21 patients with Crohn's disease as well as in 11 normal controls and 11 patients with systemic lupus erythematosus. In comparison with a control mean serum IgG1 concentration of 5173 μg/ml, patients with ulcerative colitis exhibited a significantly increased mean serum concentration of 7924 μg/ml (p < 0.05), whereas patients with Crohn's disease had a near normal mean serum IgG1 level of 5898 μg/ml. In contrast, control sera had a mean IgG2 level of 2477 μg/ml and ulcerative colitis sera had a similar IgG2 level of 2269 μg/ml, whereas Crohn's disease sera had a significantly increased mean IgG2 level of 5111 μg/ml (p < 0.05). Patients with systemic lupus erythematosus, like those with ulcerative colitis, had a markedly elevated serum IgG1 level of 15,594 μg/ml (p < 0.001) without a significantly increased IgG2 serum level (3271 μg/ml). Neither ulcerative colitis nor Crohn's disease sera exhibited altered levels of IgG3 or IgG4. These data show that alterations in IgG subclass concentrations occur in the sera of patients with active, untreated inflammatory bowel disease, similar to the previously noted changes in the IgG subclasses secreted by lymphocytes from involved inflammatory bowel disease intestinal specimens.