A sensitive RIA for human calcitonin has been developed which can detect 1-2 pg hormone. This procedure permits the measurement of the low concentrations of calcitonin in the unextracted plasma of normal human subjects. In 55 normal adults, mean plasma calcitonin was 24 pg/ml with an SD of +/- 18 pg/ml, an SE of +/- 2 pg/ml, and a range of less than 10 - 75 pg/ml. There were no discernible age or sex differences in basal hormone concentration. Infusions of calcium, pentagastrin, and glucagon stimulated plasma calcitonin, whereas food and oral calcium did not. The stimulatory effect of pentagastrin was greater in males than in females. These data demonstrate that the low concentration of calcitonin in humans can be stimulated by several secretagogues and suggest that females may have decreased calcitonin reserve.