Developmentally regulated mechanisms involving alternative RNA splicing and/or polyadenylation, as well as transcription termination, are implicated in controlling the levels of secreted μ (μ s), membrane μ (μ m) and δ immunoglobulin ( Ig) heavy chain mRNAs during B cell differentiation (μ gene encodes the μ heavy chain). Using expression vectors constructed with genomic DNA segments composed of the μ m polyadenylation signal region, we analyzed poly(A) site utilization and termination of transcription in stably transfected myeloma cells and in murine fibroblast L cells. We found that the gene segment containing the μ m poly(A) signals, along with 536 bp of downstream flanking sequence, acted as a transcription terminator in both myeloma cells and L cell fibroblasts. Neither a 141-bp DNA fragment (which directed efficient polyadenylation at the μ m site), nor the 536-bp flanking nucleotide sequence alone, were sufficient to obtain a similar regulation. This shows that the μ m poly(A) region plays a central role in controlling developmentally regulated transcription termination by blocking downstream δ gene expression. Because this gene segment exhibited the same RNA processing and termination activities in fibroblasts, it appears that these processes are not tissue-specific.