Zinc is an important mineral that is required for normal bone development. However, the direct effects of zinc on the mineralization of bone cells of human origin are not clear. The objective of this study was to determine the effects of zinc on the differentiation of SaOS-2 human osteoblastlike cells and the formation of mineralized bone nodules. Cells were cultured for 8 d and then transferred to zinc-free medium and treated with varying concentrations (0-50 microM) of zinc. Alkaline phosphatase (ALP) activity was used as a measure of osteoblast differentiation, and bone nodules were detected by von Kossa staining. After 4, 6, and 8 d of treatment, zinc increased ALP activity at 1 and 10 microM, but decreased activity at 50 microM. After 9 d of treatment, zinc increased both the number and area of mineralized bone nodules at low concentrations (1 and 10 microM), but decreased both at higher concentrations (25 and 50 microM). These findings demonstrate that zinc has biphasic effects on the differentiation and mineralization of human osteoblast-like cells.