CS-2l lymphoma cells that preferentially metastasize to lymph nodes after s.c. inoculation into BALB/c mice were grown in vitro in the presence of CA- 12 stromal cells isolated from lymph nodes. In order to obtain fundamental data on the identification and characterization of the soluble factors produced by CA-12 stromal cells, the conditioned medium of CA-12 stromal cells that inhibited apoptosis of CS-21 cells was examined. Various analytical treatments revealed that the soluble factors in CA-12 conditioned medium are very sensitive to heat treatment and trypsinization. Moreover CA-12 conditioned medium has an affinity with heparin but not with Con-A. In addition to these, the activity of CA-12 conditioned medium was blocked by H-7, a PKC inhibitor, but the conditioned medium could not induce the differentiation of thymocytes. We concluded that CA-12 conditioned medium contains stromal cell-derived apoptosis-inhibitory molecules that play an important role in proliferation of CS-2l cells by suppressing cell apoptosis.