Long-term bone marrow cultures established from C57Ks/J mice have been shown to spontaneously release endogenous ecotropic RNA type-C virus (retrovirus). C57Ks/J marrow cultures produced granulocyte-macrophage progenitor cells (GM-CFUc) and immature and mature granulocytes for over 45 weeks. In contrast, NIH Swiss mouse marrow cultures failed to release detectable ecotropic virus and generated GM-CFUc and granulocytes for 25-35 weeks and established WEHI-3 conditioned medium (CM) dependent cell lines in vitro and did not establish permanent cell lines. To determine whether viral and/or cellular genes regulated the longevity of C57Ks/J marrow cultures, groups of cultures were established from the marrow of (NIH-Swiss X C47Ks/J) F1 hybrid, F2 hybrid, and (NIH Swiss X C47Ks/J) X NIH Swiss backcross generations. Release of endogenous ecotropic virus was measured weekly in each culture as was the duration of production of immature granulocytic cells and GM-CFUc over a 58-week period. The results demonstrated a complex pattern of inheritance of longevity of long-term in vitro hemopoiesis. Increased longevity did not absolutely correlate with detectable replication of the C57Ks/J N-tropic virus.