(C57BL/Cne x C3H/Cne)F1 mice were splenectomized at 3, 9, or 19 months of age (males) or at 4 months of age (females) and observed until spontaneous death. Their mean lifespans were only slightly increased by splenectomy, but the final incidence of and age-specific death rate from reticulum cell sarcoma (RCS) were significantly decreased; the latter effect was associated with prolonged latency times of neoplastic expression. Splenectomized females had a more pronounced decrease in incidence of and rate of death from RCS than did males. Lethally irradiated male mice were inoculated with isogeneic spleen cells from young (3 mo of age) or old (12-18 mo of age) untreated male donors, and the animals surviving acute radiation effects were also observed until spontaneous death. In spite of the fact that the mean life-spans of the spleen-repopulated animals were slightly shortened, age-specific death rate analysis showed that the rate of RCS incidence approached that of untreated controls of comparable ages. The combined results of splenectomy and spleen cell transplantation strongly indicated that some cells in the spleens of these mice have a high probability of being transformed into potentially neoplastic progenitor cells with long latency between cell transformation and overt tumor growth.