Constant specific growth rate control in the methanol growth phase was investigated for the fed-batch cultivation of Pichia pastoris expressing recombinant human serum albumin (rHSA). The methanol feeding strategy was determined based on an earlier proposed macrokinetic model to maintain the specific growth rate at preset levels. The experimental results demonstrate that the control strategy of constant specific growth rate is more effective than that of constant feeding rate to maximize production. Furthermore, the most productive setpoint of the specific growth rate is found between 0.005 and 0.006 h(-1), which yields protein concentrations higher than 5 g1(-1) at 160 h. In addition, a setpoint of 0.008 h(-1) is suggested as the upper limit for specific growth rate control for the given expression system. (c) 2005 Society of Chemical Industry.