Inflammatory bowel disease is associated with a reduction in serum and red blood cell folate levels that may contribute to colonic carcinogenesis. Sulfasalazine may exacerbate such deficiencies. Indirect evidence suggests that folate supplements reduce the risk of colonic neoplasia in those using this agent, although a direct effect on colonic epithelial cells has not been shown. The aim of this study was to determine the effect of sulfasalazine and olsalamine on colonic epithelial folate levels. Epithelial cells were isolated from endoscopic colon biopsies obtained from patients with colitis who were using sulfasalazine (7 patients) or olsalamine (1 1 patients) or from controls (8 patients). The folate content of these isolates were as follows: sulfasalazine, 20.1 ? 2.55 pg/p,g DNA; olsalamine, 19.1 * 1.63 pg/pg DNA and controls 18.7 f 1.39 pg/pg DNA. Serum folate levels were reduced in the sulfasalazine group (p < 0.04). Neither serum nor red blood cell folate levels correlated with those of colonic epithelial cells. We conclude that sulfasalazine therapy administered orally is not associated with colonic epithelial cell folate deficiency. These data do not support the suggestion that the potential protective effects of folate supplements against colorectal carcinogenesis in patients with ulcerative colitis are due to correction of localized folate deficiency.