Prostanoid synthesis by cultured peripheral blood mononuclear cells and monocytes in inflammatory bowel disease patients was determined because monocytosis was reported in inflammatory bowel diseases and prostanoids are synthesized by peripheral blood mononuclear cells in response to inflammatory stimuli. Prostaglandin E2 and thromboxane B2 accumulation in the medium of cultured peripheral blood mononuclear cells isolated from patients with active Crohn's disease was two and three times higher than their respective accumulation by peripheral blood mononuclear cells isolated from normal subjects or patients in remission. In ulcerative colitis, prostaglandin E2 and thromboxane B2 accumulation was not enhanced. 6-Keto-prostaglandin F1 alpha was not detected in any of the cultured medium. The absolute number of monocytes was determined according to their adherence to plastic surfaces, and the percent of phagocytic cells was significantly higher among peripheral blood mononuclear cells in patients with Crohn's disease and ulcerative colitis as compared with peripheral blood mononuclear cells isolated from normal subjects. However, prostaglandin E2 secretion, by the same number of cultured monocytes isolated from all groups of patients, was similar. Flufenamic acid, methylprednisolone, and 5-aminosalicylic acid significantly inhibited prostaglandin E2 and thromboxane B2 accumulation. These results suggest that in Crohn's disease enhanced prostanoid synthesis is probably due to the monocytosis, whereas in ulcerative colitis the monocytosis is not accompanied by a significant increase in prostanoid synthesis in vitro.