Recent studies have shown that stem cell factor, leukemia inhibitory factor, and basic fibroblast growth factor increase proliferation and survival of the mouse primordial germ cells (PGCs) in culture. We now show that addition of tumor necrosis factor-alpha (TNF-alpha) to culture medium stimulates proliferation of PGCs without transforming them into embryonic stem cells and that its effect is specific for the PGCs at younger stages before and during their migration to gonads. A previously reported finding that TNF-alpha is expressed at these stages in mouse embryos suggests possible involvement of TNF-alpha in the proliferative regulation of the PGCs in the embryo.