Factors involved in the activity decay of an ultrafiltration reactor during the hydrolysis of hemoglobin by pepsin were studied. Biochemical and hydrodynamic parameters were assessed. The product of hydrolysis showed no inhibitory effect. Autolysis and mechanical damage of pepsin were limited by the presence of hemoglobin. Activity decay was mainly a result of the leakage of pepsin through the membrane. Electrostatic charges carried by either hemoglobin or pepsin were involved in the permeation process.