Spleen cells from C57BL mice carrying the metastatic Lewis lung carcinoma (3LL) developed a transient cytotoxic response towards the tumor shortly after tumor transplantation. Later on, the cytotoxic activity was lost and enhancing lymphocytes could be demonstrated in the spleens of the tumor-bearing mice (TBM). Spleen cells that were transferred together with tumor cells into syngeneic recipients enhanced tumor growth. The enhancing activity could be eliminated by the removal of a cell population that bound to histamine/rabbit serum albumin/Sepharose (HRS). The adherent population was enriched for enhancing lymphocytes, since it enhanced tumor growth more than the unfractionated population. The non-adherent cells, on the other hand, lost their enhancing activity in vivo and were sometimes protective against tumor growth. In addition, these cells manifested in vitro cytotoxicity against tumor cells. Hence the suppression of the cytotoxic expression in TBM is, at least in part, due to suppressor lymphocytes that bind to unsolubilized histamine. These cells seem to enhance tumor growth by suppressing host reactivity. Thus the enhancing lymphocyte populations can be separated into two subpopulations, of which one is enriched while the other is depleted of suppressor cells.