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