In biotechnological processes, foaming often represents an undesired complication. Foam may induce cell death, and may limit the performance of down-stream processing steps. On the other hand, the differences in foamability of compounds can be used for separation of these substances. The process based on this principle is called foam fractionation, and has been subject of increased attention in recent years. Foam fractionation was employed for several separation tasks, for instance, the concentration of plant secondary metabolites. However, very few studies dealt with the systematic determination of significant operating parameters and their influence on the efficiency of continuous foam fractionation processes Only. In this study, the influence of process parameters, like pH value or gas flow rate, were investigated on continuous foam fractionation of a fungal cutinase in stripping mode. Therefore, a Design of Experiments (DoE) was used to indicate significant parameters and their interactions. After the optimization of the foam fractionation process by means of the DoE, a maximal recovery of 98% active enzyme (enrichment: 5.6) or a maximal enrichment of 9.8 of cutinase (recovery: 79%) could be achieved. (C) 2011 Published by Elsevier B.V.