When B cells encounter antigen, the cells mature into terminally differentiated plasma cells and the amount of steady-state immunoglobulin (Ig) mu mRNA is increased 23-60-fold over the amount seen in earlier B cell stages. Most of this dramatic increase in Ig gene mRNA accumulation could be due to post-transcriptional regulation. We have treated a series of mouse cell lines fixed at different stages of B cell differentiation with an adenosine nucleotide analog 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) which specifically blocks synthesis of new RNA polymerase II transcripts. The amount of mu heavy chain cytoplasmic RNA, measured by quantitative Northern blot analysis at various times post DRB treatment, is reflective of the transcript's stability. The mu mRNA half-life values observed from the earliest-stage lymphomas (70Z/3 and WEHI-231) are about 1.9-4 hr, whereas the t1/2 of mu mRNA in the hybridomas (Hyb54.3C2 and IdG11) is about 13-17 hr. There is, therefore, a nine-fold maximal increase in half-life of the mu mRNA in the Hyb54.3C2 over that observed in the earliest stage (70Z/3) cells.