In this paper we describe methods for the early aetiological diagnosis of congenital hypothyroidism, using beside the classical T4, T3 and TSH plasma concentrations, four additional parameters in plasma and urine. The first one is thyroglobulin (Tg). In normal children of more than one year of age and in adults, 5-35 ng/ml plasma is found, in neonates 2-3 weeks old, this level is 10-250 ng/ml. In patients with a stimulated thyroid gland, as in primary congenital hypothyroidism, plasma Tg levels increase. High Tg values are found in iodine deficiency and in organification defects. In the absence of the thyroid gland plasma Tg is undetectable. Low to normal levels are found in cases with hypoplasia of the gland. In patients with a disturbed synthesis of Tg, resulting in Tg deficiency of the gland, plasma Tg levels vary from undetectable to normal. The PBI-T4 plasma difference, which is caused by circulating abnormal iodoproteins is the second parameter. The products of thyroidal breakdown processes of the abnormal iodoproteins are excreted in the urine and used as the third parameter. We found that the excretion of this low molecular weight iodinated material (LOMWIOM) was increased only in Tg-deficient patients. If the neonate is found to be hypothyroid, thyroid hormone substitution must be given immediately. Blood and urine sampling can be done just before or even directly after starting the therapy. The measurements extended with the determination of the total iodine excretion (fourth parameter) can be carried out within 1 week. With these additional methods it appeared to be possible to distinguish between several types of congenital hypothyroidism in neonates found by screening.