Male Sprague-Dawley rats were given graded doses of methylmercaptoimidazole (MMI), propylthiouracil (PTU), KClO4 or KI in drinking water for 4 days, or the lowest effective dose of each drug for various times. The rats were sacrificed at 1--2 p.m. and serum T3, T4 and TSH concentrations were measured by radioimmunoassays. It was found that administration of 5 mg/l of MMI, 10 mg/l of PTU and 100 mg/l of KClO4 for 4--14 days induced a transient rise in serum TSH and a fall in serum T3 or T4 or in both. The effects of KI were not consistent. In another series of experiments, PTU (10 mg/l) was given in drinking water for 4 days, and then graded doses of T3 or T4 were given iv, or 100 ng of TRH was injected into a tail vein, or the animals were exposed to 4 degrees C for 30 min. The initial high TSH levels were further increased by TRH and cold and decreased by T3 and T4. The PTU-treated animals had goitres after 4 days. We infer that low doses, that is to say 10--100 times lower than previously described, of antithyroid drugs induce a hypothyroidism characterized by an increased TSH level and a decreased serum T3 or T4 level or both. A 4 days' treatment with PTU (40 mg/l in tap water) is a suitable tool for studying the effect of various conditions on TSH secretion.