DNA helicases (Hel) play a role in a number of processes involving DNA strand separation, including replication, repair, recombination and transcription. Rearrangement of receptor genes, which occurs in immature lymphocytes, could also be mediated by Hel. We report here the cloning from murine fetal thymus tissue of a novel putative Hel containing seven conserved Hel domains and belonging to the DEGH subclass of DNA Hel. We term the encoding gene lsh (lymphoid-specific Hel), since the gene is expressed in early thymocytes, but not in heart, liver, lung, muscle, brain or kidney, as judged by Northern analysis. Spleen cells expressed lsh following activation. T- and B-cell lines, at both the immature and mature stage, expressed lsh. To examine the earliest stages of lymphopoiesis, mouse embryonic tissues were examined; lsh was not detected in the yolk sac of day 12 of gestation, but was expressed in fetal liver and at high levels in fetal thymus at day 15 of gestation.