Friend leukemia virus complex consists of a replication-competent virus plus one of two replication-incompetent viruses, spleen focus-forming virus anemia virus or spleen focus-forming virus polycythemia virus. The replication-incompetent viruses induce rapid malignant transformation of erythroid precursor cells. Transformed cell lines from mice infected with the complex can be induced to undergo erythrodifferentiation in vitro. However, lines containing the anemia-type virus require erythropoietin and another agent such as dimethyl sulfoxide for optimal erythrodifferentiation, whereas those containing the polycythemia-type virus do not require or respond to erythropoietin. Mice infected with the original Friend virus isolates were anemic, so sub-lines derived from these mice should be erythropoietin-dependent for induction of erythrodifferentiation. However, many of the widely studied sub-lines are erythropoietin-independent. In order to clarify this apparent anomaly, the genomes of viruses present in two commonly used erythropoietin-independent sub-lines were sequenced. Sequence analysis demonstrates that they contain the polycythemia-type virus and not the anemia-type virus.