To isolate novel molecules involved in intercellular signaling during mouse embryogenesis, we employed the signal sequence trap (SST) method, a newly developed strategy for cloning secreted proteins and type I membrane proteins. We constructed an SST cDNA library of mouse embryonic heart mRNA, screened 2000 clones, and acquired 1 positive clone that appeared to contain the signal sequence. Homology searches revealed that this clone encodes the mouse lymphotoxin-beta receptor (LT beta-R). The deduced amino acid sequence of the mouse LT beta-R was 66% identical to that of the human LT beta-R. Northern analysis of various organs in adult mice showed that expression levels of LT beta-R mRNA were strong in lung, liver, and kidney, moderate in heart and testis, but weak in brain, thymus, spleen, and lymph nodes. Since the mouse LT beta-R was already expressed in 7-day-postcoitus embryo, the LT beta/LT beta-R system might have some functions in early embryogenesis. We performed chromosomal mapping of the murine LT beta-R gene by linkage analysis with recombinant inbred mouse strains and found that its locus is very close to the tumor necrosis factor receptor 1 gene on chromosome 6.