A method of producing a useful high-molecular-weight substance by culturing animal cells capable of proliferation, which comprises (A) a culturing step of culturing said animal cells in suspension to form a suspension culture mixture containing the animal cells and a useful high-molecular-weight substance produced by the animal cells; (B) a separating step of separating the animal cells from the suspension culture mixture and withdrawing the culture medium; (C) a removing step of removing low-molecular-weight substances inhibiting the growth of the animal cells from the culture medium, said inhibitor substances being the metabolites of the animal cells and different from the useful high-molecular-weight substance; (D) a recycling step of recycling part or the whole of the culture medium left after removal of the growth-inhibiting low-molecular-weight substances to the culturing step (A); and (E) a recovering step of recovering the useful high-molecular-weight substance accumulated in the culture system. A culture system for culturing the animal cells is also described.