Intestinal epithelial and mononuclear cells were isolated from normal colonic mucosa and from intestinal mucosa of inflammatory bowel disease patients. Prostanoid synthesis by primary cultures of intestinal mononuclear cells were four to six fold higher than its synthesis by primary cultures of epithelial cells. Prostaglandin E2, prostacyclin and thromboxane A2 synthesis by cultured mononuclear cells isolated from inflamed ileal mucosa of four Crohn's disease patients: 5.6 +/- 1.2; 3.2 +/- 1.9 and 2.4 +/- 1.4 (mean +/- SE) ng/1 X 10(6) cells were significantly higher than their respective synthesis by cultured mononuclear cells isolated from uninflamed ileal mucosa isolated from the same patients: 0.8 +/- 0.1; 0.3 +/- 0.1 and 0.2 +/- 0.03 ng/1 X 10(6) cells or from normal colonic mucosa: 1.5 +/- 0.3; 0.3 +/- 0.1 and 0.5 +/- 0.1 (N = 12) ng/1 X 10(6) cells. Prostanoid synthesis by primary cultures of intestinal mononuclear cells isolated from colonic mucosa of five ulcerative colitis patients was enhanced but not significantly different from its synthesis by cells isolated from normal subjects. These results suggest that the enhanced intestinal prostanoid synthesis in active Crohn's disease is derived from stimulated local mononuclear cells and may have an important role in the pathogenesis of the disease.