Large doses of l-adrenaline (A), l-noradrenaline (NA) or l-isoprenaline (IPNA) increased the blood131I and plasma protein-bound 131I levels in thyroxine-blocked and in hypophysectomized but not in normal mice. The responses were similar to those of thyrotrophin, 5-hydroxytryptamine (5-HT) and dopamine (DA). It was concluded that, in the mouse, a large dose of A, NA or IPNA, like 5-HT and DA, induces a release of thyroid hormone, that this effect results from an action within the thyroid gland, and that it is not caused by intra- or extrathyroidal vascular changes. Large doses of tryptamine (TrA) and tyramine (TyA) also evoked increased blood131I levels in thyroxine-blocked mice. Thus several aromatic monoamines seem capable of inducing a release of thyroid hormone. Histamine, an aromatic diamine, was ineffective even in near-lethal doses. In thyroxine-blocked mice the alpha adrenergic blocking drug phenoxybenzamine (PhBA) inhibited the responses to A, NA, 5-HT, DA, TrA and TyA, whereas the response to IPNA was unaffected or even augmented. The beta blocking drug l-propranolol did not diminish the responses to the first six amines but inhibited the response to IPNA. d-Propranolol, which has only weak beta-blocking properties, did not affect the response to IPNA nor to any of the other amines. The alpha adrenergic blocker phentolamine inhibited the same responses as did PhBA, but also seemed to have a slight hormone-releasing effect of its own. It is suggested that, in conventional terms, the thyroid hormone-releasing effects of the biogenic monoamines 5-HT, DA, TrA, TyA, A and NA are all mediated by thyroid receptors that are similar to or identical with alpha adrenergic receptors, while the non-biogenic IPNA has a similar effect though mediated by receptors that are similar to or identical with beta receptors. Theophylline pretreatment slightly but significantly augmented the responses to both 5-HT, A and IPNA. This implies that an activation of thyroidal adenyl cyclase may be involved in the amine-induced release of thyroid hormone, whether the effect is classified as alpha or beta adrenergic in nature.