We investigated relationship between porcine skin (PS) and bovine bone (BB) gelatins in their actions on proliferation of murine benign and malignant cells in this study. We previously observed that BB gelatin enhanced spleen cell proliferation. The present study showed that such an activity of BB gelatin was not exerted in a serum-free medium. On the other hand, PS gelatin suppressed proliferation of normal spleen cells and of those stimulated by concanavalin A (Con A). It is not known whether or not such an activity of PS gelatin on Con A-stimulated spleen cells is exerted in the serum-free medium since Con A was unable to augment proliferation of spleen cells in that medium. BB gelatin as well as PS gelatin suppressed proliferation of RL male symbol 1 cells, a T cell lymphoma cell line of Balb/c mice, and such an activity of BB gelatin was not exerted in the serum-free medium whereas PS gelatin exerted its activity in the same medium. Mitomycin C (MMC)-treated spleen cells as well as MMC-treated RL male symbol 1 cells partly released RL male symbol 1 cells from the inhibition of proliferation by PS gelatin. MMC-treated RL male symbol 1 cells as well as MMC-treated spleen cells suppressed the proliferation of spleen cells augmented by BB gelatin. Inhibition of RL male symbol 1 cell proliferation by PS gelatin was not affected by BB gelatin, but enhancement of spleen cell proliferation by BB gelatin was attenuated by PS gelatin regardless of the sequence of treating the spleen cells with PS gelatin. Enhancement of spleen cell proliferation by BB gelatin was time-dependent but suppression of RL male symbol 1 cell proliferation by PS gelatin was not. In conclusion, BB gelatin enhanced proliferation of spleen cells and suppressed proliferation of RL male symbol 1 cells. In both cases, fetal calf serum (FCS) was required. PS gelatin suppressed proliferation of spleen cells and of RL male symbol 1 cells without FCS.