A functionally rearranged mu heavy chain immunoglobulin (lg) gene was introduced into the germ line of mice. The mu gene encodes a polypeptide which, combined with lambda 1 light chains, shows a specificity for binding the hapten NP. Four transgenic mice harboring 20-140 copies of the foreign mu gene expressed the gene specifically in spleen, lymph node, and thymus at a high level. Purified surface lg-positive B cells, Lyt 2-positive mature T cells, and thymocytes transcribed the foreign mu gene at a similarly high level, suggesting that control of lg gene rearrangement might be the only mechanism that determines the specificity of heavy chain gene expression within the lymphoid cell lineage. No transcription of the foreign mu gene was detected in nonlymphoid tissues with the exception of the heart which expressed the gene at a low level. The transgenic mice had up to 400-fold elevated serum levels of NP binding antibody, which contained a heavy chain with the characteristics of the foreign mu gene. The serum levels of endogenous heavy and light chains in transgenic mice appeared to be the same as in normal mice.