Na-K-ATPase has an important role in intestinal sodium and fluid absorption. We tested the colonic activity of this enzyme in patients with active ulcerative colitis to elucidate its role in the pathogenesis of the diarrhea associated with this disease. Colonic Na-K-ATPase activity in 13 patients with active ulcerative colitis prior to therapy was one-fourth of its activity in 14 normal subjects: 0.68+/-0.13 (SE) and 2.60+/-0.45 mumol/h. mg protein, respectively. In six patients with active ulcerative colitis on steroid therapy, the enzyme activity was similar to that observed in normal subjects. These results indicate an inhibition of colonic Na-K-ATPase activity in active ulcerative colitis, which may contribute to intestinal fluid accumulation and thus to the diarrhea in this disease.