Effects of triiodothyronine and the antithyroid drug, propylthiouracil, on regeneration of catecholaminergic nerve terminals in the paraventricular hypothalamic nucleus of adult rats were studied. Lesions were produced by 6-hydroxydopamine neurotoxin and then the animals were treated with triiodothyronine or propylthiouracil inducing hyperthyroidism or hypothyroidism, respectively, as determined by radioimmunoassay. Although catecholaminergic varicosities increased with time in the paraventricular hypothalamic nucleus of rats after lesion, fluorescent microscopic quantitation showed no statistical difference in their number between rats treated with triiodothyronine and the vehicle for as long as 56 days. Furthermore, electron microscopic quantitation at 56 days postlesion showed no significant difference between the triiodothyronine-treated and control rats in terms of the density, proportion, size, types of synapses, and synaptic frequency of catecholaminergic nerve terminals. There were growth cones in the paraventricular hypothalamic nucleus, suggesting growth activity after lesion. However, we found that exogenous administration of large doses of triiodothyronine at 25 micrograms/kg had little effect on the enhancement of regeneration of central catecholaminergic terminals after their destruction by 6-hydroxydopamine.