Modulation of the growth of human and murine cell lines in vitro by recombinant human tumor necrosis factor-α (rTNF-α) and recombinant human interferon-γ (rIFN-γ) was investigated. rTNF-α had cytostatic or cytolytic effects on only some tumor cell lines. When administered together with rIFN-γ, rTNF-α showed enhanced antiproliferative effects on a subset of the cell lines tested. In contrast to its effects on sensitive tumor cells, rTNF-α augmented the growth of normal diploid fibroblasts. Variations in the proliferative response induced by rTNF-α were apparently not due to differences in either the number of binding sites per cell or their affinity for rTNF-α. These observations indicate that the effects of rTNF-α on cell growth are not limited to tumor cells, but rather that this protein may have a broad spectrum of activities in vivo.