Interleukin‐1 (IL‐1) enhances bone resorption and formation in vitro, presumably through a primary action on osteoblasts, but the mechanism by which IL‐1 activates bone cells is unknown. We investigated the possibility that the effect of IL‐1 on osteoblasts is mediated through an increase in intracellular calcium [Ca++]i by studying the effects of purified human monocyte‐derived IL‐1 (hIL‐1) and recombinant human IL‐1α (rhILα) and β (rhIL‐1β) on [Ca++]i in the rat osteogenic sarcoma cell line UMR 106 using indo‐1, a new‐generation fluorescent Ca++‐sensitive probe. hIL‐1 (1 U/ml) resulted in an 85.5% rise in [Ca++]i over baseline that reached a peak after 30 seconds and returned to basal levels within 60 seconds. A similar transient rise in calcium was obtained upon exposure of the UMR cells to both the hIL‐1 suspension buffer and to the concentration of fetal bovine serum present in the hIL‐1 buffer. This effect was not abolished either by heat inactivation of both hIL‐1 and serum or by pretreatment of hIL‐1 with specific rabbit antihuman‐IL‐1 antibody. Moreover, exposure of the UMR cells to either rhIL‐1α or rhIL‐1β or to a mixture of both at concentrations of 1 to 100 U/ml was not followed by any change in [Ca++]i. Our data do not support the idea that IL‐1 can stimulate osteoblasts through a calcium‐mediated pathway.