Random fecal alpha 1-antitrypsin levels were determined in 34 patients, 24 with Crohn's disease, and 10 "controls" having diarrheal illnesses not associated with intestinal protein loss, in an effort to evaluate its usefulness as a measure of Crohn's disease intestinal activity. In the control group, all alpha 1-antitrypsin levels were less than 2 mg/g dry wt of stool. The mean fecal level among those with Crohn's disease was 52.9 mg/g (range less than 2 to greater than or equal to 200). There was a strong correlation between disease activity, as measured by a clinical score, and the alpha 1-antitrypsin levels (Spearman r = 0.65, p = 0.001). This correlation was similarly strong among those with colitis or ileitis. A fecal value greater than 20 mg/g may provide a rough guideline to separate patients with clinically active disease from those with inactive Crohn's disease, despite a considerable range of fecal levels among patients with a particular clinical score. Fecal alpha 1-antitrypsin levels correlated with several other laboratory measures that have been proposed as indicators of Crohn's disease activity. The serum orosomucoid, C-reactive protein, and albumin correlated with the clinical activity score among some of our patient groups. Both clinical scores and laboratory parameters, however, may have limited usefulness in a variety of circumstances. Random fecal alpha 1-antitrypsin determinations seem to provide a reliable, although not directly quantitative, measure of the intestinal activity among patients with Crohn's disease, especially when other methods may be inconclusive.