The human genome contains a family of endogenous retroviruses, HERV-K, with sequence homology to the B-type mouse mammary tumor virus. We have now identified a single HERV-K LTR within the C-type-related human retroviral element S71. The HERV-K LTR is located in the antisense direction between the S71 gag and the pol gene, replacing the 5' half of S71 pol. A number of HERV- K LTR-related cDNA clones were detected by screening various human cDNA libraries with an S71 HERV-K LTR probe, indicating abundant transcription of HERV-K-related LTRs in human tissues. Sequence analysis of four cDNA clones revealed LTR sequences with a nucleotide identity of 70 to 90% with HERV-K10 LTR. Some HERV-K-related LTR sequences contain potential short open reading frames. The analyzed cDNA clones do not harbor any retroviral sequences other than those related to HERV-K LTRs. However, most of the solitary LTRs were found to be coexpressed with cellular sequences. Transcription of these LTRs is probably directed by external cellular promoters. We show that HERV-K LTR- like sequences entered the primate genome about 33-40 million years ago. We estimate the human genome to contain about 25,000 copies of HERV-K-related LTRs, which are distributed over most human chromosomes in an irregular manner.