To elucidate possible physiological functions of human endogenous retroviruses (HERVs) and their role in the pathogenesis of human diseases, we have developed a strategy to identify transcriptionally active HERV genes. By this approach, we have identified and isolated an active HERV-E gene that was mapped to 17q11. Although the gene was predicted to produce no intact viral particles due to the presence of stop codons, long open reading frames were retained in each gag and pol region. Northern blot analyses revealed in the pancreas (and thyroid) two major transcripts, 3.3 and 4.1 kb in size, associated with 500-to 600-nucleotide-longer minor bands. Preferential expression in pancreas and thyroid gland tissues may suggest a role for this gene in physiological functions common to these tissues.