Supernatants of cultured spleen cells (SCS) from small-tumor-bearing mice (STBM) and large-tumor-bearing mice (LTBM) were tested in vivo by their ability to modify tumor development. We found that when inoculated with S13 tumor cells into the foot-pad of syngeneic normal BALB/c mice, SCS enhanced tumor growth as well as accelerated tumor takes. When STBM and LTBM were operated on, the persistence of the enhancing activity by SCS was found to be associated with tumor size at the time of tumor removal. As early as 24 hours after small-tumor resection, enhancing activity disappeared or diminished to undetectable levels. On the other hand, enhancing activity by SCS from large-tumor-resected mice (LTRM) persisted until 15 days after surgery, and then faded. Enhancing activity associated with SCS from S13-tumor-bearing mice (TBM) was also seen when injected with M3 cells, a syngeneic unrelated tumor. Normal SCS did not affect tumor development. It seems that the rate of disappearance of enhancing activity observed in SCS from S13-tumor-resected mice (TRM) is mainly dependent on the size of tumor burden at the time of surgery.