The effects of nutrient depletion and toxic by-product accumulation on the viability of hybridoma cells and monoclonal antibody production were investigated for the purpose of increasing the productivity of monoclonal antibodies in large-scale cultivation of hybridoma cells. Maximum concentration of ammonia produced during the culture was found to be 35 ug/ml, which had detrimental effect on the cell growth and antibody production. Lactic acid itself showed very slight toxic effect on the cell viability and antibody production, while accumulation of lactic acid decreased significantly the pH of the culture broth which had detrimental effect on the cell growth. The optimal pH for the cell growth and antibody production was found to be near 7.3. Below and beyond this physiological pH, both cell viability and antibody production decreased. It was also found that the effect of toxic by-product accumulation, mainly ammonia, was more significant rather than nutrient depletion on the cell viability, although these two factors had integrated effect. Reduction of fetal calf serum level from 10\% to 5\% did not affect significantly the cell growth and antibody production whereas below 5\% of fetal calf serum cell growth and antibody production were reduced significantly, and without fetal calf serum cells did not grow. By supplement of 1\% Nutridoma-sp to culture media after the adaptation of cells for 3 months through serial transfers of cells from the medium with high fetal calf serum to that with low fetal calf serum, it was finally possible to reduce the concentration of fetal calf serum to 1\%, at which cell and antibody yield were comparable to those obtained in media containing 10\% fetal calf serum.