The murine 4-1BB gene, encoding a member of the nerve growth factor/tumor necrosis factor (NGF/TNF) receptor family, is thought to be selectively expressed in T cells and is involved in the regulation of lymphocyte proliferation. We detected two forms of the 4-1BB mRNA by RT-PCR which were expressed in an activation-dependent pattern in splenocytes and thymocytes. cDNA sequencing showed that the smaller form was a mRNA splice variant lacking the transmembrane region (4-1BB delta TM), because of the deletion of exon 8. The two forms of mRNA are differentially expressed in murine T cells, macrophages, 3T3 fibroblasts and epitheloid cells. Northern blotting also identifies two forms of mRNA of 1.5 and 2.4 kb, and the cell-type-specific pattern correlated with the PCR results. These results identify a novel form of 4-1BB. This and the previously known membrane-associated form have a broad tissue distribution, suggesting a more diverse role in host defense.