We have identified and characterized a human endogenous retrovirus (HERV) gag transcript in the human pre-B cell leukemia line Reh. The transcript was found to be a splice product of a structurally intact HERV element located on chromosome 6q13. Its primer binding site is complementary to phenylalanine (F) tRNA, common for the HERV-F family, but the overall genome sequence is closely related to the HERV-H family. The retroviral sequence was therefore designated HERV-H/F. The HERV element shows a distinct mRNA expression pattern among hematopoietic cancer cell lines with expression in some leukemia-derived cell lines of B-lymphoid and myeloid origin. No expression was observed in normal human tissues, indicating a cancer-specific expression pattern. The 5' long terminal repeat (LTR) was tested for promoter activity in HERV-H/F expressing and nonexpressing cell lines. The cell specificity of the LTR-mediated reporter gene expression did not conclusively correlate with endogenous virus expression, indicating that the transcription regulation of this gene is not alone dependent on cell-specific activity of transcription factors.