We applied sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting to analyze fecal alpha 1-proteinase inhibitor (alpha 1 PI) from healthy subjects and patients with Crohn's disease. A component with Mr 38,000 was characterized in normal fecal extracts as well as in six pathological samples. In these cases, the Crohn's disease activity index (CDAI), a clinical index of severity of the disease, was 170 (SEM 47). In contrast, alpha 1 PI of Mr 51,000 was detected in fecal extracts from eight patients with active Crohn's disease (CDAI = 287, SEM 39). We conclude that fecal alpha 1 PI can be considered a marker of intestinal disease activity.