Hybridomas with non-growth-associated antibody production are thought to exhibit enhanced specific monoclonal antibody productivity (q(MAb)) when subjected to hyperosmotic stress. Two hybridoma cell lines exhibiting non-growth-associated antibody production, S3H5/γ2bA2 and DB9G8 hybridomas, are cultivated in a batch mode using hyperosmolar media resulting from sodium chloride addition. Their response to hyperosmotic stress regarding q(MAb) is quite different, though they show similar depression of cell growth in hyperosmolar media. The q(MAb) of S3H5/γ2bA2 cells in a hyperosmolar medium (396 mOsm/kg, 10% fetal bovine serum (FBS)) is enhanced by approximately 180% when compared with that in a standard medium (283 mOsm/kg, 10% FBS), while q(MAb) Of DB9G8 cells in the same hyperosmolar medium is enhanced by only 10%. Thus, the enhanced q(MAb) of hybridomas exhibiting non-growth-associated antibody production resulting from hyperosmotic stress is cell line-specific.