Serum lysozyme (muramidase) activity was determined by the Lyso-Plate diffusion technic in 419 subjects consisting of normal persons and patients with Crohn's disease, ulcerative colitis, nonspecific diarrhea and various other disorders. Lysozyme activity in the normal subjects did not exceed 37.8 microgram/ml. The values in the several groups of patients overlapped markedly with each other and with the normal range. Approximately two-thirds (62.1%) of the 37 patients with Crohn's disease had values that were within the normal range. In about half (51.8%) of the patients with this disease in whom the process was clinically active, serum lysozyme activity was increased. Of 10 patients with Crohn's disease who had undergone resection, heightened serum lysozyme activity was found only in the three patients in whom there was clinical evidence of recurrence of the disease. It is concluded that serum lysozyme activity is not a dependable means of distinguishing Crohn's disease from ulcerative colitis or nonspecific diarrheas. The determination would appear to be of value, however, in helping to identify activity, recurrence, or extension of the disease in patients with Crohn's disease.