The effects of calcitonin (CT) and histamine on calcium metabolism in the hepatic bile system of rats were investigated. The subcutaneous administration of CT (20 and 80 MRC mU/100 g) to rats caused a significant fall in serum calcium and a marked increase in liver calcium. The subcutaneous administration of histamine (0.1 mg/100 g) to rats produced a significant decrease in serum calcium, while it did not significantly alter liver calcium. However, the effects of CT (20 or 80 MRC mU/100 g) on the serum and liver calcium was markedly prevented by the simultaneous administration of histamine (0.1 mg/100 g). On the other hand, the excretion of calcium into the bile of thyroparathyroidectomized rats intraperitoneally injected with the calcium chloride (4.0 mg Ca/100 g) was markedly increased by the administration of CT (20 or 80 MRC mU/100 g) or histamine (0.1 mg/100 g). Reversely, a remarkable elevation of bile calcium by CT was clearly prevented by the simultaneous administration of histamine (0.1 mg/100 g). The present results further support the point of view that the hypocalcemic effect of CT is based on the stimulation of calcium excretion into the bile by the hormone.