The introduction of cloned foreign genes into cultured mammalian cells1–7 has been used to identify DNA sequences required for correct transcription in vivo8–10. It is not clear, however, to what extent these systems will be useful for an analysis of the sequences necessary for tissue-specific gene expression. A more appropriate approach for such an analysis might be the production of mice that contain a cloned foreign gene in all their cells, throughout development. This could be accomplished by the transfer of a cloned gene into germ-line cells, and the subsequent transmission of that gene to offspring. Previously, SV40 DNA sequences11 and a cloned HSV-1 thymidine kinase gene12 have been introduced into somatic tissues of mice by microinjection of the DNAs into blastocysts11 or eggs12, but germ-line transmission of these sequences has not been demonstrated. The only foreign DNA sequences which have been transferred into and transmitted by the mouse germ-line have been exogenous Moloney leukaemia virus genomes introduced by viral infection of early embryos13. We now report the introduction of a cloned rabbit DNA fragment containing the adult β-globin gene into the germ-line of mice. We have analysed 24 mice derived from eggs microinjected with this DNA. Nine mice contain the rabbit β-globin gene in liver DNA, and at least four males from this group transmit the gene to a fraction of their progeny.