Gallium nitrate is an effective antihypercalcemic and antiresorptive agent. Although its effects on osteoclasts are well documented, the mechanism of action of gallium nitrate on osteoblasts is still not established. To determine the effects of gallium nitrate on calcium signalling, we studied its effects on intracellular calcium concentration in UMR-106 rat osteoblastic osteosarcoma cell line. Cells were loaded with a calcium binding fluorescent dye, fluo-3. Changes in fluorescence reflected changes in cytosolic calcium. Gallium nitrate elicited a dose-dependent biphasic calcium transient with an initial decrease followed by an increase, and these changes were seen at high extracellular calcium concentration. Markedly altered signal was seen in nominal calcium-free medium, suggesting that gallium nitrate mobilized calcium only partly from intracellular stores. Gallium nitrate, at concentrations as low as 3 micrograms/ml, inhibited parathyroid hormone-stimulated calcium transients. High doses of parathyroid hormone could overcome this inhibition. This inhibitory effect appears to be selective, since gallium nitrate did not prevent calcium transients elicited by alpha-thrombin or prostaglandin F1 alpha. Failure of gallium nitrate to prevent calcium transients elicited by these agents, even after the inhibition of parathyroid hormone-induced signal, indicates that the inhibition is not a toxic effect. In conclusion, gallium nitrate has a marked effect on calcium signalling in UMR-106 cells that might be of major importance in modifying the effects of calcemic hormones or local factors on osteoblasts.