Abstract: The present invention provides methods of producing recombinant fibrinogen in a long-term mammalian cell culture system. Disclosed is a method for the production of recombinant fibrinogen, comprising: growing mammalian cells that express recombinant fibrinogen in a serum-free medium for a time of at least one month at a level of at least 5 .mu.g/ml; and then collecting portions of the conditioned medium at least twice during the culturing time of at least one month, with each portion containing at least 5 .mu.g/ml of recombinant fibrinogen. Also disclosed is a method for the production of recombinant fibrinogen, comprising: growing mammalian cells that express recombinant fibrinogen in a serum-free medium at a level greater than 1 .mu.g/ml; collecting at least a portion of the conditioned medium, and then purifying the fibrinogen from the medium by anion-exchange chromatography or affinity chromatography.