MUC2 is the predominant mucin in the human colon responsible for the protective mucus layer. We developed methods to quantify MUC2 biosynthesis, which were used to study the regulation of MUC2 expression in the colon of normal individuals and of patients with ulcerative colitis. Colonic biopsies were metabolically labeled, and biosynthesis of MUC2 precursor was quantified using SDS-PAGE. Total MUC2 and MUC2 mRNA were quantified using blotting techniques. MUC2 precursor biosynthesis and total MUC2 levels were significantly decreased in ulcerative colitis patients with active inflammation compared to controls. In contrast, both these parameters returned to control values during remission of the inflammation, demonstrating that colonic biosynthesis and total amounts of MUC2 vary according to the activity of the disease. However, MUC2 mRNA levels were similar in all patients and independent of disease activity, indicating that these variations in MUC2 synthesis are post-transcriptionally regulated.