Calcitonin (CT) deficiency and its possible repercussions on bone mass were studied in a group of 9 adult patients (7 females, 2 males) with congenital hypothyroidism of dysgenetic origin. Using a new extraction, method (exCT) which considerably improves the sensitivity and the specificity of the assay for CT-monomer, we measured CT levels before and after a short calcium (Ca) stimulation test (2 mg Ca/kg over 5 minutes) to evaluate C-cell secretory reserve. Mean basal plasma CT concentrations were lower in the hypothyroid women (mean±SEM:0.6±0.1 pg/ml) than in 30 normal female controls (1.7±0.2 pg/ml,P<0.001). Serum calcium increased similarly in the two groups, but postinfusion CT levels were lower in the hypothyroid women, (1.7±0.2 pg/ml) than in normal women (16.8±2.9 pg/ml),P<0.001. Hypothyroid women showed a 10% reduction in bone mineral content at the diaphyseal site in the radius, 0.840±0.037 g/cm, compared with normal age-matched controls, 0.930±0.020 g/cm, (P<0.05). Our study demonstrates the existence of a profound CT-monomer deficiency in adult patients with thyroid agenesis or dysgenesis. Both calcitonin deficiency and thyroid hormone treatment could play a role in the observed bone loss. Attention should therefore be paid to bone metabolism during treatment of congenital hypothyroidism to avoid further bone loss.