Hybridomas with non-growth-associated antibody production kinetics are thought to be exhibit enhanced specific monoclonal antibody productivity ($q_MAb$) when subjected to osmotic stress. Two hybridoma cell lines, S3H5/γ2bA2 and DB9G8 hybridomas were cultivated in a batch mode using DMEM-based hyper- and hypoosmolar media resulting from addition and subtraction of NaCl, respectively. The $q_MAb$ of S3H5/γ2bA2 cells under hyperosmotic stress (433 mOsm/kg) was increased by 80%. Besides $q_MAb$, $q_glc$ and $q_lac$ were also rather increased under hyperosmolar condition. In hypoosmotic range, $q_MAb$ was not changed significantly, and $q_glc$ and $q_lac$ were decreased as the osmolality decreased. Specific growth rates and maximum MAb titres are gradually decreased as the osmolality went far away from the control value (327 mOsm/kg). DB9G8 cells also show enhanced $q_MAb$ (by 98%) under hyperosmotic stress (436 mOsm/kg). However, $q_glc$ were $q_lac$ are not increased with the increase in osmolality. The basal media used also influenced the cellular responses to hyperosmotic stress. DMEM, IMDM, RPMI 1640 have different composition with one another. RPMI 1640 contains less amounts of most ingredients compared with DMEM or IMDM. S3H5/γ2bA2 cells showed increased $q_MAb$ under hyperomotic stress regardless of media used. However, DB9G8 cells exhibited quite different responses to hyperosmotic stress regarding $q_MAb$. Thus the enhanced $q_MAb$ is cell-line specific and basal media-specific.