A rotary membrane separation system was used in a continuous fermentation of Pichia pastoris with cell recycling to obtain high cell concentration and high thrombomodulin production. The dilution rates of this continuous fermentation were between 0.25 and 0.35 dm(3) day(-1), and the production process was maintained for 10 days. Since cells were recycled and only part of liquid broth was taken from the system, a very high cell concentration level (248 g dm(-3)) was obtained. The peak protein expression level was at 72 h after methanol induction, was 300 mg dm(-3) (3.6 x 10(5) activity unit cm(-3)) and the total harvested supernatant was three times the working volume.