The high cell density fermentation of recombinant Pichia pastoris for human serum albumin (HSA) production is a high oxygen demand process. The oxygen demand is usually met by increased agitation rate and use of oxygen-enriched air. However, fermentation using a microbubble dispersion (MBD) can supply adequate oxygen to the microorganisms at relatively low agitation rates because of improved oxygen mass-transfer of the microbubbles used for the sparging. Conventional air-sparged fermentations were conducted for the production of HSA using P. pastoris at agitation rates of 350, 500, 750 rpm. These experiments were compared to MBD-sparged fermentation at 350 and 500 rpm agitation rates. After 97 It of air-sparged fermentation, cell masses were 27.9, 48.9, and 138.2 g/l at agitation rates of 350, 500, and 750 rpm, respectively. For MBD-sparged fermentation, cell mass concentrations after 97 It were 129.9 and 137.7 g/l at 350 and 500 rpm, respectively. Protein concentrations were 36.3 and 67.8 mg/l for air-sparged at 350 and 500 rpm, while 267.3 and 301.2 mg/l for MBD-sparged experiments at 350 and 500 rpm, respectively. The volumetric oxygen mass-transfer coefficient, k(L)a for the MBD system at 500 rpm was 268.6 h(-1) compared to 76.1 h(-1) for the conventional sparger at 500 rpm. There was significant improvement in oxygen transfer to the microorganism relative to the conventional sparger. (c) 2004 Elsevier Ltd. All rights reserved.