Among the 10(5) LINE-1 sequences (L1Hs) in the human genome are one or more 6-kb segments that are active retrotransposons. Expression of these retrotransposons appears to be favored in cells of germ line origin, as well as in some other tumor cells of epithelial origin. In such cells, the product of the first L1Hs open reading frame (ORF), a protein called p40, is detectable; p40 has no apparent similarity to gag proteins, but contains a leucine zipper region which may be responsible for the occurrence of p40 multimers. Transcription of L1Hs initiates at residue 1 although the transcriptional regulatory regions are downstream in the first 670 bp of the 5' untranslated region; deletion of a YY1-binding site in the first 20 bp reduces transcription by fivefold. Translation of the second ORF, which encodes reverse transcriptase, is independent of the translation of the frame encoding p40.