The effects of varying the initial calcium and phosphate concentrations of the culture media on bone calcium and phosphate release were examined, using whole calvaria from 3-day-old mice in 48-hour cultures. The initial calcium and phosphate concentrations of the culture media were varied in the range 3-10 mg/100 ml; either calcium or phosphate alone was changed while the other ion was held constant, or the concentrations of both were varied while the Ca:P ratio was held constant. For all combinations, 3 treatment groups were used: i) control (no added hormone); ii) 0.5 U/ml PTH; iii) 50 mU/ml CT. The release of calcium and phosphate from the bones was greatest at low initial calcium or phosphate concentrations in the media, and least at high initial concentrations. High concentrations of both ions together abolished hormonal responses and resulted in extensive uptake of calcium and phosphate by the bones. The response to PTH was lost at a high concentration of either ion alone, while a response to CT was observed under all experimental conditions except simultaneously high calcium and phosphate concentrations.