Immunoglobulin (Ig) synthesis, natural killer (NK) cell activity, and lymphokine production by peripheral blood mononuclear cells (PBMC) were studied in 34 patients with ulcerative colitis (UC). Levels of Ig produced by PBMC were significantly higher in patients with active UC as compared to controls. However, there were no significant differences in Ig-synthesis between patients with inactive UC and controls. NK cell activity was significantly decreased in patients with active UC as compared to controls, and a significant negative correlation was observed between the level of IgA and NK cell activity in patients with UC. Reconstitution experiments demonstrated that CD56+ cells from controls suppressed the levels of IgA, when added to the culture containing a constant number of B cells and CD4+ cells. In contrast, CD56+ cells from patients with active UC completely lacked the capacity to suppress IgA production. In addition, the activities of interleukin-2 and interferon-gamma were significantly decreased in patients with active UC. The present study suggests that immunoregulatory abnormality of NK cells exists in patients with UC and impaired NK cell activity may be related to increased Ig-synthesis observed in these patients.