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Improvement of alpha interferon (IFNα) production was attempted using recombinant E. coli by optimizing fermentation conditions. A protocol that ensures an increased productivity of IFNα mostly in active, soluble form without affecting the growth activity of cells was devised. Although the cells grew well in a neutral medium, a slight decrease in medium pH,i.e. to pH 6.7, resulted in a significant increase in the production of soluble IFNα. The growth activity and total IFNα productivity were not altered by a change in fermentation temperature in the range of 30-37℃. Ratio of soluble form to inclusion body increased with decreasing temperature, with over 90% of total interferon being of soluble form when cultivated at 30℃. An increase in the nitrogen concentration of Terrific Broth-based medium supplemented with L-leucine gave remarkably improved results. A fermentation protocol derived from these observations enabled us to enhance the productivity level of IFNα over 200 x 10 exp (8) IU/-broth by 14h fermentation.