Recombinant human interferon‐α2C and recombinant human interferon‐γ(5–1000 U/ml) inhibit the proliferation of normal human bone‐derived cells and a human osteosarcoma cell line. In the bone‐derived cells the inhibitory effect of interferon‐γ was significantly greater than that of interferon‐α, whereas in the osteosarcoma cell line the inhibitory effects of both interferons were quantitatively similar. Interferon‐α did not affect the alkaline phosphatase activity of either type of cells. In contrast, interferon‐γ affected the activity of the enzyme in both cell types: in the bone‐derived cells the effect of interferon‐γ was stimulatory whereas in the osteosarcoma cells the effect was inhibitory. In both cell types interferon‐γ selectively inhibited the incorporation of radiolabelled proline into type I collagen. In the osteosarcoma cells, the effects of both interferons on collagen synthesis were quantitatively similar. In the bone‐derived cells, however, interferon‐α decreased proline incorporation into collagen and non‐collagen proteins to a similar extent and thus did not affect collagen synthesis when expressed as a percentage of total protein synthesis.