Both l-thyroxine and d-thyroxine induced an inhibition of glucose-induced insulin secretion with comparable time-and dose-dependent characteristics. l-thyroxine was ten times more potent than d-thyroxine. While l-thyroxine and a ten times higher dose of d\ x=r eq-\ thyroxine had a similar potency in inducing hyperthermia and hypocholesterolaemia, hyperglycaemia in response to d-thyroxine was less pronounced than in response to l-thyroxine. This difference may be explained by a greater depletion of liver glycogen stores and consequently more limited capacity for provision of glucose for the circulation. The results support the view that the differences between l-thyroxine and d-thyroxine are quantitative. Adrenergic contribution to l-thyroxineand d-thyroxine-induced inhibition of insulin secretion by rat pancreas is apparently of minor importance. Treatment of the rats with propranolol as well as with reserpine or 6-hydroxydopamine did not alleviate l \ x=r eq-\ thyroxine-or d-thyroxine-induced inhibition of insulin secretion by rat pancreas. Thyroid hormones decrease glucose tolerance and may induce diabetes in animals and in man prone to the diabetogenic action of thyroid hormones (Houssay 1948). L-Thyroxine as well as L-triiodothyronine are known to inhibit insulin secretion by the pancreas in rats and mice (Lenzen 1978; Len¬ zen & Klöppel 1978).p-Thyroxine has a biological activity much lower than that of the l.-isomer. The ratios between biological activity of D-thyroxine and L-thyroxine, however, vary greatly (Starr 1978). It has been claimed that D-thyroxine in contrast to l.-thyroxine is able to lower plasma cholesterol levels without concomitant increased blood glucose concentra¬ tions (Starr 1978).In the present investigation, time-and dosedependent effects of l.-thyroxine and D-thyroxine on glucose-induced insulin secretion by perfused rat pancreas were compared. We have used a specially pure preparation of D-thyroxine (Neudecker & Scheiffele 1971) to exclude the possibility of contamination with L-thyroxine.Hyperthyroidism increases sensitivity for catecholamines and many metabolic effects of thyroid hormones can be reproduced by application of catecholamines (Himms-Hagen 1967). In the pre¬ sent experiments, the contribution of the adrener¬ gic nervous system to the effects of i.-thyroxine and D-thyroxine on insulin secretion was studied by application of drugs which affect the adrenergic nervous system. Materials and MethodsChemicals i.-Thyroxine (sodium salt) and D-thyroxine (sodium salt, containing only 0.05% L-thyroxine and 0.5% D-triiodothyronine) (Neudecker & Scheiffele 1971) were kindly provided by Henning