Industrial filamentous fungal fermentations are typically operated in fed-batch mode. Oxygen control represents an important operational challenge due to the varying biomass concentration. In this study, oxygen control is implemented by manipulating the substrate feed rate, i.e. the rate of oxygen consumption. It turns out that the setpoint for dissolved oxygen represents a trade-off since a low dissolved oxygen value favors productivity but can also induce oxygen limitation. This paper addresses the regulation of dissolved oxygen using a cascade control scheme that incorporates auxiliary measurements to improve the control performance. The computation of an appropriate setpoint profile for dissolved oxygen is solved via process optimization. For that purpose, an existing morphologically structured model is extended to include the effects of both low levels of oxygen on growth and medium theological properties on oxygen transfer. Experimental results obtained at the industrial pilot-scale level confirm the efficiency of the proposed control strategy but also illustrate the shortcomings of the process model at hand for optimizing the dissolved oxygen setpoints. (c) 2007 Elsevier Ltd. All rights reserved.