Endogenous retroviruses (ERVs) constitute a significant fraction of the mouse and human genomes, approximately 10% and approximately 8%, respectively, and they are transmitted to offsprings in a Mendelian fashion. Recent reports implicated that certain ERVs participate in a range of disease processes. In this study, we examined injury-elicited changes in murine ERV (MuERV) expression in lymphoid tissues and characterized biological properties of the putative MuERVs isolates. Female C57BL/6J mice were subjected to approximately 18% total-body-surface-area burn injury. Four different lymphoid tissues (blood, bone marrow, spleen, and thymus) were collected at 24 h for reverse transcriptase-polymerase chain reaction analysis of MuERV expression by amplifying the 3' U3 regions. Within each tissue examined, there was a unique pattern of injury-elicited changes in MuERV expression. From the 17 unique MuERV U3 clones isolated from all four tissues, nine were derived from injury-induced MuERVs, four from injury repressed, and four from no change. A survey of the C57BL/6J genome using all 17 U3 clones as probes produced 26 pertinent putative MuERVs, of which five were presumed to retain intact coding potentials for essential polypeptides. Biological properties (genomic location, tropism, transcriptional potential, coding potential, primer-binding site, recombination, and integration age) of each putative MuERV were characterized, and their relevance to injury response was discussed. The findings from this study suggest that injury-elicited stress signals either induce or repress specific MuERV populations in a lymphoid tissue-specific and probably cell type-specific manner. It warrants a further investigation into the roles of the injury-responsive MuERVs in postinjury pathogenic processes of the immune system.