In the present study, we have shown that insulin-like growth factor-I (IGF-I) was released by primary cultures of rat osteoblast-like (ROB) cells into the conditioned medium (CM). Dexamethasone (DEX) caused a dose-dependent inhibition of the IGF-I. At 10(-8) M, DEX reduced IGF-I level to 70% of the control value (P < 0.05); at 10(-7) M DEX, the IGF-I level was further reduced to 60% of the control (P < 0.01). The active vitamin D metabolite 1,25-dihydroxycholecalceferol [1,25(OH)2D3] slightly increased the IGF-I level, but the increase was not statistically significant. However, in combined treatments of 10(-7) M DEX and 10(-8) M of 1,25(OH)2D3, the inhibition of DEX was partially antagonized by the presence of 1,25(OH)2D3. Studies with metabolically radiolabeled IGF-I by immunoprecipitation indicated the changes of IGF-I in the CM reflected synthesis of the protein by the cells. The alteration of IGF-I level may mediate some of the actions of these steroid hormones on bone cells.