Lactate dehydrogenase (LDH) derived from rabbit muscle enhanced IgM production by human-human hybridoma HB4C5 cells 12.4-fold at 320 mug/ml under serum-free conditions. LDHs from pig muscle and pig heart also accelerated IgM production 8.4- and 6.4-fold, respectively. The immunoglobulin production stimulating activity of LDH was not accompanied by activation of cell proliferation. LDH from rabbit muscle facilitated IgM and IgG production by human peripheral blood lymphocytes. This means LDH stimulates immunoglobulin production not only by the specified hybridoma cell line, but also by unspecified immunoglobulin producers. LDH from rabbit muscle enhanced IgM production of transcription-suppressed HB4C5 cells treated with actinomycin D. The immunoglobulin production-stimulating factors (IPSFs) effect of LDH was slightly weakened by sodium fluoride (translation inhibitor) treatment of HB4C5. Moreover, the amount of intracellular IgM of monensin-treated HB4C5 cells was obviously enhanced by LDH. This result means that the IPSF effect of LDH is irrelevant to the post-translation activity of target cells. It is expected from these findings that LDH from rabbit muscle accelerates the translation step to enhance immunoglobulin productivity. The immunoglobulin production-stimulating activity of LDH was inhibited by colchicine, endocytosis inhibitor. This fact suggests that it is necessary for LDH to be taken by target cells to act as an IPSF.