A depth filter perfusion system (DFPS) for animal cell culture was developed and its use in continuous high-density cultures of hybridoma cells was investigated. In the DFPS, based on cell immobilization in a cylindrical depth filter matrix, cells were easily immobilized a nd cultivated by simple medium recirculation. The cell density in the 20-mu m pore size filter matrix reached up to 3 x 10(7) cells/mL in less than 10 days. This resulted in a high monoclonal antibody productivity of 744 mg/L/day, which was 25-35 times higher than that of continuous-suspension cultures using the same cell line. The 20-mu m pore filter retained more cells than the 30-mu m filter in a shorter period. The DFPS provides advantages of low-cost set-up, easy operation, and scale-up in the cultures of anchorage-independent cells. It also has a high potential for anchorage-dependent cell cultures because of its unusually high surface-to-volume ratio of 450-600 cm(2)/cm(3).