Here we report a survey of c-rel proto-oncogene transcription in murine tissues, cell lines and lymphoid cells. In addition to the previously described 7.5-kb mRNA, we have identified a mRNA of 2.5-kb. As DNA hybridization indicates that there is only one gene with significant homology to c-rel in the mouse genome, it appears that multiple mRNAs are transcribed from c-rel. The nucleotide sequence of a cDNA clone derived from the 2.5-kb c-rel mRNA demonstrates that the 7.5- and 2.5-kb mRNAs encode identical proteins. The different size of the two mRNAs is due to variation in the length of the 3' untranslated region, which arises from the use of alternate polyadenylation signals. These mRNAs are present at low levels in organs tested, and in cell lines representing a wide variety of lineages. Fibroblasts are the only cells in which expression was not detectable. In B-cell lines representing different stages of differentiation, the highest levels of mRNA are seen in B-lymphomas, and this level drops markedly in plasmacytomas. There is a transient increase of 10- to 20-fold in the level of c-rel mRNAs in T-cells treated with concanavalin A, while lipopolysaccharide-stimulated B-cells exhibit a transient 5-fold elevation of c-rel expression. This study indicates that the control of c-rel expression can vary between and within different cell lineages, and the widespread expression of this gene points to a fundamental cellular function, rather than one restricted to hematopoietic cells as previously suggested.