Background: To evaluate the diagnostic use of fecal concentrations of lactoferrin (Lf), calprotectin (Cal), polymorphonuclear neutrophil-elastase (PMN-e), and lysozyme (Lys) as indicators of disease activity in patients with active and inactive ulcerative colitis (UC). Methods: A total of 76 fecal specimens were collected from 31 patients with UC in times of active and inactive status of disease. Disease activity was determined with the colitis activity index (CAI; Rachmilewitz index), which includes a combination of laboratory parameters and clinical symptoms, with a score of at least 6 indicating active disease. Fecal Lf, Cal, PMN-e, and Lys were measured and reported as micrograms per milliliter feces. Levels of more than 7.25, more than 6.00, at least 0.062, and at least 0.6 for Lf, Cal, PMN-e, and Lys, respectively, were considered elevated as specified by the manufacturers. Results: Based on the CAI classification, 25 of the samples were from patients with active disease status and 51 were from patients with inactive status. Lf, PMN-e, and Cal but not Lys showed increased levels in samples from patients in active disease compared with those in remission (median for Lf: 28.12 ± 110.86 versus 179.54 ± 334.09, P < 0.001; median for Cal: 15.13 ± 30.27 versus 116.23 ± 182.29, P < 0.001; median for PMN-e: 0.21 ± 0.44 versus 1.02 ± 0.89, P < 0.001; median for Lys: 1.54 ± 2.39 versus 3.75 ± 5.39, P > 0.05). All 4 parameters correlated with the CAI (Lf: r = 0.441, P < 0.001; Cal: r = 0.505, P < 0.001; PMN-e: r = 0.604, P < 0.001; Lys: r = 0.295, P < 0.05). Introducing a composite index based on Lf, Cal, and PMN-e, the specificity was 72.5% and the sensitivity 88% compared with the CAI. Conclusions: Among the neutrophil-derived proteins in feces, PMN-e, Cal, and Lf represent useful markers of disease activity in patients with UC. Using all 3 markers in a composite index may be an additional noninvasive tool for the management of ambulant patients with UC.