A lactulose/mannitol (La/Ma) test was compared with a standard cellobiose/mannitol test (Ce/Ma) in 17 patients with newly diagnosed celiac disease and 12 healthy controls. The mean La/Ma test was 0.163 (SEM 0.076) in celiacs and 0.016 (SEM 0.002) in controls. The mean Ce/Ma test was 0.132 (SEM 0.024) in celiacs and 0.014 (SEM 0.002) in controls (p less than 0.001). There is no significant difference between the new La/Ma test and the Ce/Ma test. Eighty-two patients referred to a general gastroenterology clinic with symptoms or signs of celiac disease performed a La/Ma test. A jejunal biopsy was indicated in 44 of these. In this selected group the sensitivity was 89%, specificity 54%, and negative predictive value of 95%. The La/Ma test fulfills the criteria of a screening test; it is sensitive, of low cost, and simple to perform, and it has the advantage of a simple enzyme assay and does not cause diarrhea in patients with hypolactasia. It can, therefore, be used in screening large patient populations.