Endogenous calcitonin was altered in rats by thyroparathyroidectomy, followed by supplementation with thyroxine and calcium. As a result, a reduction in the content of 5-hydroxytryptamine in the brain together with an increase in the concentration of tryptophan in the plasma were observed. The changes were accompanied by a diminution in the activity of both choline acetyltransferase and acetylcholinesterase in the cerebral hemispheres. The results are consistent with those produced by exogenous hormone and suggest that calcitonin probably plays a role in the regulation of 5-hydroxytryptamine levels in the brain.